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Part IV: Understanding Vaccine Safety

This is the last blog piece in this blog series, as I wrap up my coverage of the most recent ACIP meeting. It has become clear that many people, even some of the members of this committee do not understand vaccine safety, what it means when we say a vaccine is “safe,” and how we determine whether a vaccine is “safe.”

Before we begin, I have followed very closely what anti-vaccine (when I refer to anti-vaccine, I mean those who purposefully distort, twist, and misrepresent vaccine information with an agenda to serve their own ideological, political or financial interests through misleading and manipulating the public; I am not referring to vaccine skeptics, those who have been misled by anti-vaccine activists; and those who are just confused by all of this) doctors and others in positions of power or influence say and write to pick up common themes and strategies for confusing the public. Here are some warning signs that you may be reading and listening to anti-vaccine propaganda:

1. Statements about vaccines that are infused with inflammatory language, e.g., “crimes against humanity,” or violations of the “Nuremberg Code.” These statements are intended to conjure up images of the horrible, unethical treatment and experimentation on prisoners, especially twin children, by Dr. Josef Mengele in Nazi concentration camps, and wholly inappropriate to our current day clinical trials with human subject protections. Scientists have science to back us up; we do not have to resort to hyperbolic and inflammatory language.
2. Continued claims about vaccines as being experimental. Although, as you will see below, vaccines are experimental (i.e., under an investigational new drug (IND) designation following an application to the FDA) until the Phase I, II and III clinical trials are successfully concluded, once application is made to the FDA in a biologics license application (BLA) and the FDA experts and committees have completed their review and granted the vaccine a biologics license, they are no longer experimental. At this point all of the COVID-19 vaccines currently available in the U.S. are licensed and these vaccines are no longer investigational or experimental.
3. Claims that the mRNA vaccines are “gene therapy.” Gene therapy refers to treatments we can offer for some diseases that are caused by a single gene abnormality, e.g., sickle cell anemia and Huntington’s disease (just recently reported). That is completely different than an mRNA vaccine that couldn’t possibly alter your genes and anti-vaccine advocates use this phrase to try to make people think that their DNA is being altered if they receive the vaccine, which is absolutely untrue.
4. Statements that go something like this: “X vaccine has caused more deaths than the disease” it is intended to prevent. That is a sure-fire sign that the person is not serious. In recent history, the FDA has suspended or revoked licensure for vaccines that have caused less than a handful of serious adverse events or deaths (e.g., the J&J COVID-19 vaccine and the lxchiq chikungunya vaccine) that were dramatically less than the number of deaths caused by the diseases for which they were intended.
5. Inconsistencies. These are the result of some of the most common tactics that I see today, including this one that was offered by a member at the recent ACIP meeting. Statement A – “We shouldn’t recommend a vaccine until we have evidence that it is 100 percent safe.” Statement B – “We don’t need to wait until we have 100 percent evidence of effectiveness for (fill in the blank with ivermectin/hydroxychloroquine/a supplement they are selling/other).”

We often speak about safety in daily life and often make statements about things being safe. Usually when someone says that some activity is safe, it doesn’t mean that no one has ever been harmed by the activity or never could be in the future, but rather that the chances of harm are so low and/or the magnitude of the harm is low enough that the risk of harm is below the tolerance level for harm relative to the benefit of the activity to whoever is making the judgment that the activity is “safe.”

So, here is an example from my life. I have a friend who jumped off the side of a mountain cliff on a bungee cord and who went base jumping (i.e., jumped off a high bridge with a parachute), and filmed both events for me to see. He obviously is a thrill-seeker. No one has ever accused me of being a thrill-seeker. I do enjoy a good roller coaster ride, but, probably 30 years ago, with each of my daughters on either side of me, an amusement park lifted us up on a platform that we were lying down on as if we would fly like superman. We were to pull a cord when the lift stopped that would release us from the lift and allow us to free fall joined together and attached by a bungee cord. When we got as high as the lift was going to take us and they instructed us to pull the cord, I was paralyzed with fear and unable to pull the cord. One of my daughters did the deed for us. I have never done that again.

He invited me to go with him the next time he goes cliff or base jumping and I have politely declined. He considers both activities “safe,” but in his case, he gets a benefit out of it that for him outweighs the risks – a thrill, the sense that he has accomplished something that most other people have not, boasting rights, a sense of accomplishment and overcoming his fears, etc. So, he has a different lens for his risk-benefit analysis than I would. For me, the analysis goes like this-  On the benefit side: I have nothing to prove, I would be absolutely terrified rather than experiencing a thrill, I have plenty of other accomplishments, so in my estimation, the benefit of doing either of these activities is 0, in fact, probably a negative number in that the travel and time to do either of those activities means I would most likely give up a day of doing other things that to me would be more enjoyable or a productive use of my time. As for the risks, these are not well defined, because there is no registry, but there is one report that I found that the risk of death could be as high as 1 in every 2,317 jumps.

But let’s look at common every day risks that the majority of people still consider “safe activities.” Most people, including safety experts, consider commercial air travel “safe.” In the past 10 years, the number of deaths per year in the U.S. from commercial airline crashes in in single digits. Last year, it was zero. This year, it is unusually high surpassing 60 deaths. In the last survey I could find, 44 percent of Americans flew commercially just in 2022 and ninety percent of Americans reported having ever flown commercially. Obviously, the vast majority of Americans consider commercial air travel safe. Likely, they all have made the calculation that the benefit of travelling by air – whether allowing them to get somewhere that might be more difficult or impossible by other modes of transportation or by allowing for faster travel, made the risks of travel acceptable in their minds.

Many gun owners consider guns to be safe, even though they understand that there are significant risks with guns.

With all of these activities – base jumping, commercial air travel, and owning guns – what is “safe” is also different under different conditions and allows for mitigations or risk. For example, the risks of base jumping significantly increase when the weather is windy. Thus, the relative risks can be reduced by clear weather with low winds (however, I am still not going). With commercial air travel, risks are mitigated through regular maintenance of airplanes, safety inspections, coordination of flights by air traffic controllers, and intense safety training for pilots and flight attendants. Gun ownership risks can be mitigated with gun safety training and utilizing gun safes in homes with children.

Most of us don’t give significant thought about the risks of getting in the car to go to work, to visit friends and family or to go to other destinations (in 2022, there were 5,930,496 vehicle crashes that were significant enough that the police were called, or roughly 16,248 crashes per day). This is a case in which society agrees that your “freedom” to drive a car must be under some restrictions for the well-being of all of us. The states require all drivers to be of a certain minimum age that increases the likelihood we will be responsible and competent drivers. Each state requires licensure to drive and compliance with speed limits, stop signs or lights, and other restrictions on drivers, and every state restricts the freedom of drivers to be impaired in their driving from alcohol or drugs. Most drivers consider themselves to be “safe” and consider driving to be “safe” because it is a very convenient way for us to get to places we need to get to and we assume that because we are safe drivers and that other drivers will for the most part comply with traffic regulations, that we are unlikely to be in one of the 16,248 crashes that day.

In fact, it is hard to think of anything that is entirely, 100 percent safe. Some toys warn of the hazards of choking. Some packaging warns of the risks of suffocation if that packaging is put over a person’s head. People have drowned in their bath tubs. There are slightly less than 300 unlucky Americans that get struck by lightening every year.

So, too, when we say a medication or a vaccine is “safe,” we are not saying that nothing bad has ever happened or never will. Like all of the above, safe is a determination made after comparing the benefits against the risks. A common strategy of those who spread vaccine disinformation is to emphasize or exaggerate potential harms and, in some cases, to fabricate those harms, while dismissing or downplaying the benefits. Let me be clear here: misleading patients into believing that any medication or vaccine is perfectly safe is just as manipulative and improper as misleading patients into believing that a medication or vaccine that has been approved for use for a particular condition is all risk and no benefit for treatment or prevention of that condition.

Under the Public Health Services Act that sets the criteria for the FDA in determining whether medications and vaccines are safe, the word “safety” means “the relative freedom from harmful effects, direct or indirect, when a product is prudently administered, taking into consideration the character of the product in relation to the condition of the recipient at the time.” The word “relative” means relative, or in comparison, to the disease or condition that the medication is intended to treat or the vaccine is intended to prevent. Thus, if the FDA is asked to approve a medication that is miraculous and causes a self-limited (meaning that it will go away on its own and not get worse or cause complications) itchy rash overnight, but causes a fatal cancer in 5 percent of those who use the medicine, then that is not a safe medication because there is no chance of dying from the rash and no chance that the rash would cause a fatal complication, thus this is a case where the cure is worse than the disease.

On the other hand, if the FDA is asked to approve a medication for a rare cancer of children that eventually takes the lives of those children in 100 percent of cases and for which we have no current therapies, and this new medication cures 90 percent of the children, but can cause an incurable blood cancer in 5 percent of these cured children, the FDA would likely determine that this medication is safe (because safety is determined relative to the disease it is treating), even though this is a dangerous medication in that it itself can cause incurable cancer and obviously, you would not want to administer this medication to children who don’t have this rare cancer. In the same manner, a “safe” medication such as ivermectin (because it is highly effective in treating certain tropical parasitic diseases, with far milder health consequences than the untreated parasitic diseases for which it is therapeutic) would not be “safe” when used to treat certain viral illnesses because the accumulated scientific studies demonstrate a lack of effectiveness against these viruses (especially SARS-CoV-2) so the benefit is 0, while there is a percentage of people who will experience adverse effects from the medication.

How do we ensure Vaccine Safety?

The FDA Safety and Innovation Act (FDASIA) of 2012 requires vaccine manufacturers to submit a Pediatric Study Plan early in the development process for any vaccine that will be used in children. The initial plan must contain an outline of the study or studies that the sponsor plans to conduct that includes study objectives and design, age groups to be tested, relevant end points (end points are the measures to determine success – e.g., prevention of severe disease and death), and the statistical approach to be used.

The FDA’s Center for Biologics Evaluation and Research (CBER) regulatory staff consists of a multidisciplinary team of scientists, medical officers, and regulatory and public health professionals, including formal advisory committees, including experts in the fields of vaccinology, microbiology, infectious diseases, immunology, biostatistics, epidemiology, and clinical trial design.

Before a vaccine is ever approved, CBER will review the biochemistry, manufacturing, controls information, the manufacturing facility and equipment; preclinical and clinical data on the safety, efficacy, pharmacology, and toxicology; the suitability of the clinical trial design, and the analysis of the clinical data derived from the clinical trial(s). CBER scientists review research in the areas of statistical and epidemiologic analysis.

The sponsor (usually the manufacturer) must first obtain an investigational new drug (IND) designation for its candidate vaccine. Once the FDA staff have done the above reviews, determined that the regulatory requirements have been met and that the anticipated potential harms to subjects in the planned clinical trials are reasonable under the circumstances and to be fully disclosed by the plan sponsor, the vaccine candidate can receive the IND designation and the investigational phase may begin.

The investigational phase actually consists of three phases of trials. Phase I clinical trials are primarily aimed at providing the initial evaluation of safety and immunogenicity (the immune response resulting from the vaccine candidate). Phase I trials are typically conducted on a small number (usually 20 – 80 in a first attempt to identify common adverse events, which are those that occur at a rate of more than 1 per hundred subjects) closely monitored, healthy, non-pregnant adult volunteers. If the vaccine is intended for use in children, then the Pediatric Study Plan will most often call a series of these Phase I studies that progressively step down in age to the first age of life if no serious safety events occur and if the vaccine continues to be satisfactorily immunogenic in the older age groups.

Phase II clinical trials generally follow successful phase I trials with larger groups of subjects (often several hundred or more and now begin to identify some of the rare adverse effects, meaning those that occur at a rate of less than 1 per hundred subjects), usually in a randomized, controlled methodology. In addition to continuing to monitor for safety and assurance of adequate immunogenicity, the studies are often structured to test for the optimal dosage that allows for a reduction in dose so long as immunogenicity can be maintained. Phase II studies may or may not begin to also examine vaccine effectiveness against one or more endpoints (infection, symptomatic infection, severe illness, hospitalization, or death).

Phase III studies are begun after satisfactory results from Phase II trials and involve many more subjects (often thousands or tens of thousands) and more data is obtained regarding safety, immunogenicity, vaccine effectiveness, and at this point may begin to test for the safety and efficacy of the vaccine in combination with other vaccines that might be anticipated for coadministration (e.g., COVID-19 + influenza vaccines). Phase III trials would generally use our most rigorous study methodology – randomized, double-blind, well-controlled studies. Sometimes, investigators may also be able to explore the issue of immune correlates of protection, i.e., what level of immune response (generally antibody titers) are usually associated with protection from the end-point being measured.

If the results of Phase I, II and III investigational clinical trials are favorable, the vaccine may progress to the licensing phase after the sponsor or manufacturer submits a biologics license application (BLA). CBER’s multidisciplinary team of experts will review all the materials submitted, review the investigational clinical trials design and the results. In addition, the manufacturing facility will be inspected. CBER will often then convene its advisory committee, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) to review the data and offer recommendations as to the information that will eventually go into the package insert if the vaccine is granted a biologics license.

If approved by the FDA, the matter is then, most often, taken up by the CDC’s experts to study the vaccine’ approval, safety and immunogenicity and then convene its committee of outside experts, the Advisory Committee on Immunization Practices (ACIP), to make recommendations regarding the ages, timing, and frequency of administration of the approved vaccine that become effective if and when the CDC Director signs off on them.

At this point, the vaccines will generally have coverage by Medicare, the Children’s Health Insurance Program (CHIP), small and individual market plans and the Vaccines for Children Program (VCP) that reflects the recommendations signed off by the CDC Director.

At this point, post-licensure and post-marketing adverse event monitoring will begin. There is a sophisticated interrelated system of vaccine safety monitoring in the U.S. Before I explain this system, let’s get a few concepts down.

Side effect – these are commonly occurring, time-limited, and usually local reactions that generally occur within minutes to hours following the vaccination. Common examples are redness at the injection site, soreness at the injection site, and swelling at the injection site. Other examples that are not local reactions include fever, muscle aches, and fatigue, most often improving, if not resolving, by the second day.

Adverse events – these unexpected reactions that can range from minor to life-threatening, and that oftentimes require medical attention and evaluation.

Background rates of conditions – An effective tool to help us sort our safety signals from coincidence, especially with new vaccines.

Vaccine Adverse Event Reporting System (VAERS) 

The Vaccine Adverse Event Reporting System (VAERS) is administered and operated by the FDA and CDC jointly. “Its primary function is to detect early warning signals and generate hypotheses about possible new vaccine adverse events or changes in frequency of known ones.” https://pubmed.ncbi.nlm.nih.gov/15071280/. VAERS, however, is highly misused and misrepresented by anti-vaccine advocates. They pull reported data from VAERS and try to make claims about numbers of deaths or any number of other adverse events that they attribute to vaccines; however, incidence rates and relative risks of specific adverse events cannot be calculated from the data in VAERS. That is because anyone can report to this database, but the public’s view of data only portrays data that has not been verified (it comes from raw data).

Those who misuse and abuse the raw data from VAERS in an attempt to discourage or scare others from getting vaccinated generally take every report at face value without questioning the self-reported diagnosis and with the assumption that every death reported is a vaccine death instead of accounting for background rates of mortality and whatever other reported conditions they wish to exploit. Let me explain.

Let’s look at the month of April in 2021. Recall that the mRNA vaccines (Pfizer and Moderna) were given emergency authorization in the fall of 2020 and were rolled out starting in late December, primarily to health care providers. In early 2021, eligibility was gradually expanded as vaccines increasingly became available, and in the first few months of that year, priority was generally given to the elderly (>65 years old). In early April 2021, around the time most states expanded vaccine eligibility to include all adults, more than two million people were receiving their first vaccine each day. https://www.usatoday.com/in-depth/graphics/2021/01/14/covid-vaccine-distribution-by-state-how-many-covid-vaccines-have-been-given-in-us-how-many-people/6599531002/. Let’s assume then a rate of roughly 2 million people receiving the COVID-19 vaccines. I am going to use 2019 data as to the average number of daily deaths in the U.S. so as not to reflect any deaths from COVID-19. In 2019, just short of 8 thousand people died per day. https://www.consumershield.com/articles/how-many-deaths-every-day-us. Now the 2 million people getting vaccinated per day is not evenly distributed across all age groups, because none of the vaccines were being administered to children and adolescents at that time, and of course, deaths are not evenly distributed across all age groups, as we know a person’s risk of dying increases significantly after age 65. Further, 8 thousand deaths per day, is simply the background rate of mortality among Americans; obviously, with a pandemic that was causing many deaths, especially among those over age 65, one would reasonably expect the number of deaths to be higher. But, those who wanted to create alarm and vaccine distrust, attributed every death reported in VAERS as caused by the vaccines without accounting for the fact that roughly 8,000 people in the age groups being vaccinated were expected to die daily, not even adjusting for the death rates in these age groups from COVID-19 infection itself.

The way that VAERS is intended to work and how the CDC and FDA evaluate its data is to look for safety signals – adverse events are being reported that are unexpected and in a higher number of people than would be expected based on the background prevalence of that condition or disorder, when CDC and FDA are alerted by the reports of the adverse event examine multiple vaccine monitoring sources. If a safety signal is identified, the CDC and FDA will then conduct a hypothesis testing study to examine the incidence of the adverse event risk after vaccination. Many times, the safety signal is not verified or validated after an investigation of the reported cases is undertaken. On occasion, and this happened with one of the non-mRNA vaccines, a safety signal was verified, and even though its occurrence was so uncommon that it would not have shown up until millions of people were vaccinated, the severity was such that its use was paused and then physicians were notified not to offer the vaccine except in those cases where the patient wanted to be vaccinated, but could not or would not take one of the mRNA vaccines, and was advised of the risk. Once we had another authorized vaccine that could serve as an alternative, the non-mRNA vaccine at issue was pulled from the market.

When a safety signal is verified, teams of researchers begin work to identify the biologic mechanisms of the adverse event and look for strategies to prevent the adverse event.

The CDC’s Immunization Safety Office monitors vaccine safety through other monitoring systems in addition to VAERS. These include VSD, CISA, and V-safe.

VSD is the Vaccine Safety Datalink. It is a collaborative model for high-quality vaccine safety data, unlike VAERS. VSD is provided data from 13 integrated healthcare systems covering more than 15.5 million people per year including sites on both coasts and in middle and midwestern states. Active monitoring and chart reviews for vaccine adverse events are based only on health care professional input in the medical records of patients. Rapid monitoring occurs for pre-specified events as well as for unexpected adverse events. This system allows for quick detection and assessment of safety signals. The VSD provides CDC and FDA experts with much richer data and information than is available through VAERS only, including links to vaccination records, individual patient characteristics and health care visits, whether these occur in clinic settings, emergency rooms or in-hospital. VSD allows for weekly sequential monitoring of possible adverse events with rapid cycle analysis surveillance. Whereas VAERS will potentially alert us to a safety signal, VSD is designed to detect statistically significant safety signals. VSD allows analysts to compare adverse events among vaccinees in the same age group, gender, race/ethnicity and geographic location. It also allows for comparison of a detected potential adverse event in the first 21 days following vaccination (the time interval in which most adverse events occur) to a comparator group of other vaccinees up to 63 days post-vaccination. VSD detected a safety signal for ischemic stroke following the Pfizer bivalent booster in patients age 65 and older in October of 2022. Monitoring in other vaccine safety systems did not reveal an ischemic stroke signal, and with investigation and further monitoring, the evidence became clear that this safety signal was not verified.

The CDC’s Clinical Immunization Safety Assessment (CISA) Project, established in 2001, is a national network of vaccine safety experts from the CDC, eight medical research centers and other partners that can provide consultation to public health and healthcare providers about complex vaccine safety questions relating to individual patients (these consultations are offered free of charge), and who can conduct clinical research studies to better understand vaccine safety and find preventive strategies for adverse events following immunization. The clinical experts include the disciplines of infectious diseases, neurology, allergy, immunology, pediatrics, hematology, and obstetrics/gynecology.

V-safe is a program that has enrolled more than 10 million participants and sends them periodic check-ins via test or email to monitor how they feel following vaccination, even if the person is experiencing no signs or symptoms.

Together, these four vaccine safety monitoring systems give the CDC and FDA a lot of information from various perspectives from people of all ages and across all parts of the country. These systems have surprised me in their ability to alert CDC and FDA staff when only a hand-full of serious adverse events have triggered a safety signal with vaccines.

Part III: The COVID-19 Vaccines

The Issue – Given the sudden dismissal of all former members of the ACIP, the recent replacement of these members, and the firing of the CDC Director, there was a need for the ACIP to issue its recommendations for the recently FDA-approved 2025 – 2026 Updated COVID-19 vaccines.

What were the considerations before the committee?

The ACIP needed to provide its recommendations to the CDC Director (currently the Acting CDC Director since the CDC Director was just recently terminated for refusing to agree to approve the ACIP recommendations in advance of them being made) on who is recommended to get the updated COVID-19 vaccines (generally based upon age and underlying medical conditions) as this would provide guidance to health care providers, the public, and determine coverage for the recommended vaccines by Medicaid, CHIP, ACA-compliant health plans, and the Vaccines for Children (VFC) program.

What was the recommendation put before the committee by the chair to be voted upon?

Unfortunately, there were four votes that would ultimately be called for, but these were not provided to the public in advance, and it appears likely that no one other than the chair of ACIP and the chair of the COVID-19 Vaccine Work Group knew what the four recommendations would be until the very end of the meeting.

As a consequence, the discussion of the COVID-19 vaccines was meandering, at times got into technical information that I would be very surprised if more than a couple of the committee members understood what the presenters were presenting; veered back and forth between data and facts to anecdotes, case reports, misinformation and pure speculation; and in the end, resulted in a series of recommendations from the Work Group with a separate minority report from other members of the Work Group who strongly disagreed with the Work Group’s recommendations.

The recommendations that were put to a vote were:

Vote #1 (but they actually considered this second) Passed 11-1-0

CDC should consider adding language accessible to patients and providers to disclose the six risks and uncertainties included in the Work Group presentation (benefits of seasonal boosters are of modest benefit and short duration; evidence that repeated seasonal mRNA boosters cause acquired changes in the immune system and may be associated with increased vulnerability to future infection, including SARS-CoV-2 and other respiratory viruses, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and suppressed immune surveillance including immune fatigue or suppression that is currently not well understood; there are documented deaths from symptomatic and subclinical myocarditis, pericarditis and potentially other cardiovascular conditions post-vaccination, including of healthy children with probable causal relationship to mRNA vaccines; post-vaccine syndrome; persistence of spike protein and lipid nanoparticles; the safety and efficacy of COVID-19 vaccine during pregnancy have never been tested in appropriate randomized clinical trials. In one randomized trial, there was observed numerical imbalance of a higher number of babies with congenital malformations from vaccinated mothers).

Vote #2 (this was actually the third vote to be taken) 6-6-0 Failed

State and local jurisdictions should require a prescription for administration of the COVID-19 vaccines.

Vote #3 (this was actually the fourth vote to take place) Passed 12-0-0

Health care providers should discuss the risks and benefits of vaccination for individual patients.

Vote #4 (this was actually the first item voted upon) Passed 12-0-0

The pediatric and adult immunization schedules for approved COVID-19 vaccines should be updated as follows:

• Adults 65 and older – vaccination based upon individual-based decision-making.
• 6 months of age – 64 years – individual-based decision-making with emphasis that the risk-benefit of vaccination is most favorable for individuals at increased risk for severe COVID-19 disease and lowest for those individuals who are not at increased risk.

My Take

One of these decisions was bad; one was mixed good and bad (perhaps even all good -see below); one was good; and one was irrelevant.

Let’s start with the vote that failed. This was a good decision. Had it passed, this would provide that states should require a prescription for administration of the COVID-19 vaccines. First of all, it is not the jurisdiction of ACIP to determine whether a vaccine should require a prescription, nor is it the ACIP’s providence to tell states what they should do.

Had this recommendation passed and the acting CDC director signed off on it, it would significantly impede access to the vaccine. In the most recent year, 90 percent of COVID-19 vaccines were administered by a pharmacist. However, many states do not permit pharmacists to write prescriptions. Thus, many people who wanted to be vaccinated would need a prescription from their physician or nurse practitioner, and I would not be surprised if many practices required the patient to come in for the counselling about the vaccine (see below) and the prescription. This would lead to delays in getting the vaccine and costs for deductibles and co-pays. Further, the way the recommendation was presented, it would mean that seniors and immunocompromised patients who would be recommended to get two vaccines per year (and potentially more for the later group) would need a prescription twice a year, even though the patient and doctor had already concluded previously that the patient’s age and/or underlying health conditions warranted the vaccine. For all of these reasons, this recommendation would just put more barriers in the way of getting the vaccine and discourage some patients from making the effort.

Let’s dispense with Vote #3, which was actually the last vote to be held. This is the irrelevant one. The discussion of risks and benefits is already a legal duty for any health care provider who is administering a vaccine.

Let’s now deal with what was supposed to be Vote #1, but turned out to be the second voting item.

The new ACIP committee is operating under a number of misguided approaches to vaccine science, clinical trial design, and the doctrine of informed consent. I’ll address some of these as they relate to this vote.

First, the informed consent doctrine is based upon disclosing the risks and benefits of the intervention, including those associated with not undergoing the procedure, that a reasonable, prudent physician similarly situated would disclose (some jurisdictions) or that a reasonable patient would want to know (other jurisdictions). No court that I am aware of has ever held that a physician must disclose every known risk, no matter how rare or unlikely, and certainly not risks that are not known.

A fundamental ethical principle behind informed consent (autonomy on the part of the patient) is that the health care provider should not present the risks and benefits in an unbalanced manner so as to manipulate the patient into agreeing to or refusing a procedure so as to serve the best interests of the health care provider as opposed to the best interests of the patient. What I observed by listening in to these two days of meetings is that the discussions themselves were disproportionately focused on considering all real and imagined harms from vaccines, while spending almost no time trying to identify even all of the real benefits from those vaccines.

One can see even from the wording of this recommendation that it only mentions disclosing six additional “risks and uncertainties,” without any mention of fully disclosing the additional benefits of vaccination besides the primary ones of reducing the risk for severe illness and death.

The first such “risk” to be disclosed is that the benefits of seasonal boosters are of modest benefit and short duration. First of all, it is a bit ironic that a group that holds itself out to be vaccine scientists and experts refers to the “seasonal” vaccine as “boosters.” Boosters are a repeated dose of the same vaccine in order to “boost” the immune response generated by the prior dose of that same vaccine. The newly approved COVID-19 vaccines that these recommendations address are actually new formulations of the vaccines that are based upon more recently circulating variants, and thus, they are “updated” vaccines rather than “boosters.” Further, the statement is misleading. In children under age 2 years and adults over age 65, the benefits are more than modest. So far the COVID-19 vaccines have provided only short-term reductions in the risks of transmission and infection, but very durable and prolonged protection against severe disease, especially the most severe of the severe forms of COVID-19.

The next “risk or uncertainty” to be disclosed is “evidence that repeated seasonal mRNA boosters cause acquired changes in the immune system and may be associated with increased vulnerability to future infection, including SARS-CoV-2 and other respiratory viruses, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and suppressed immune surveillance including immune fatigue or suppression that is currently not well understood.” This statement seems clearly calculated to unduly scare people and to avoid acknowledging that any of these risks are far more likely in the setting of infection rather than vaccination. First, “evidence that repeated seasonal mRNA boosters cause acquired changes in the immune system” (I am not going to repeat my criticism of their terminology) can best be addressed by a response I sometimes get from my grandkids – “duh!” The reason we give vaccines is to cause the immune system to acquire changes, specifically we expose the immune system to, in the case of the COVID-19 vaccines, one of the virus’ key proteins so that the body can recognize it, hopefully before it is exposed to the actual infectious virus, and have a head start in making antibodies that interfere with the ability of the virus to infect our cells, as well as make memory cells so that in the future, when exposed to infectious virus, it doesn’t take our body as long to make antibodies (and the antibodies that we do make are often broader and better), and also so that we develop T-cells that trained to recognize infected cells so as to destroy those cells, thereby ridding us of and clearing the virus from our bodies.

That same risk statement goes on to state ”and may be associated with increased vulnerability to future infection, including SARS-CoV-2 and other respiratory viruses, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and suppressed immune surveillance including immune fatigue or suppression that is currently not well understood. Now, I know what they are talking about, but I doubt that any health care provider who doesn’t spend every waking hour studying this stuff the way I have would have any idea what they are talking about. They are referring to inconsistent findings that some persons will demonstrate a class switch in their antibody response (this is very complicated and technical, and so I am not going to go into detail here unless I get a lot of comments asking me to explain this in detail) after repeated vaccination. What this refers to is that we actually make many different classes of antibodies in response to an exposure. Some class switches are quite typical and normal, e.g., generally, we make IgM antibodies in the first week of infection that are generally replaced over the next week or weeks by IgG (due to a class switch), and this is very beneficial for reasons that I am not going to expound on right now. What the Work Group is referring to is a different class switch, which occurs in some people after the initial class switch from IgM to IgG in which subclasses of IgG switch (there are four subclasses of IgG, which fortunately are called IgG 1, IgG2, IgG 3 and IgG 4) and what the Work Group is pointing to is an increase in the relative proportion of IgG 4 antibodies in these individuals after repeated vaccination. They suggest that this class shift “may be associated with increased vulnerability to future infection, including SARS-CoV-2 and other respiratory viruses, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and suppressed immune surveillance including immune fatigue or suppression that is currently not well understood. First of all, I think I have read every paper that has been published on this phenomenon, and I am not aware of one instance where investigators have demonstrated that those with this class shift have demonstrated any of these adverse immunological or other health effects. I am going to ask all of the immunologists reading this to please forgive my overly simplistic generalization of the immune system here, but for all my other readers, I suggest that you can think of the immune system as too little being bad (for example people who have immune deficiencies) and too much being bad (e.g., the cytokine storm that we have previously discussed in the second week of severe disease in adults or the MIS-C I have previously written about in children). Its really all about getting enough of an immune response soon enough, without getting an overreaction of the immune response. Vaccination increases the likelihood of both of these conditions being met. Now, I have previously written about parts of the immune system that make sure we get enough of a response and in time. Those include the innate immune system, cytokines and chemokines (we have especially discussed interferons), and antibodies. We all have IgG4 in our blood (unless your have an immunodeficiency where you can’t make them), and generally its role is thought to be largely in constraining that immune response and making sure that we get enough, but not too much. There is some suggestion that IgG4 may be protective against developing Long COVID since some studies have found that after SARS-CoV-2 infection, those who went on to develop Long COVID had a much lower proportion of IgG4 than those who recovered from COVID-19 without developing Long COVID.

Where I think that the Work Group came up with this list of harms is that there are rare diseases for which IgG4 is central to the illness and is present in far greater proportions, e.g., IgG4-related disease and IgG4 autoimmune disease, which may manifest with some of these features. However, these conditions are completely unrelated to vaccines. I also am not aware of any evidence that repeated vaccination would actually increase your risk for COVID-19, in fact, I think the weight of the evidence would argue for exactly the opposite. While, I could write more on this, let me just close on this particular item by pointing out that “immune fatigue” is not a thing. I don’t know if the Work Group was confused and was referring to chronic fatigue syndrome or perhaps T-cell exhaustion, but frankly neither one of those would make any sense to me. Obviously, if they are not making any sense to me, it doesn’t seem like this is a good idea for the ACIP to be specifically asking busy health care providers to explain this to patients before they vaccinate them.

The next risk they offer is “there are documented deaths from symptomatic and subclinical myocarditis, pericarditis and potentially other cardiovascular conditions post-vaccination, including of healthy children with probable causal relationship to mRNA vaccines.” This is one of the best examples of a violation of the principles of informed consent. If I saw you in the office and determined that you had high blood pressure and needed to start you on medication, but I didn’t explain the risks of not treating your high blood pressure and only spent the time reviewing all the terrible and rare potential adverse effects that could occur with taking the medicine, my guess is that you might not be inclined to take the blood pressure medicine. Here there is no explanation that myocarditis and pericarditis occur more frequently and more severely in people with COVID-19 than in people who receive the vaccine. Second, if this is referring to the same case reports that I am thinking of, it was two children and the causal link is not established. When we start talking about “healthy children” dropping dead from the vaccine without context, without evidence, and without quantifying it, it seems intended to alarm and frighten more than inform.

At the end of the sentence, the Work Group has actually identified a big problem that I have with their recommendations – “causal relationship to mRNA vaccines.” Even if the “causal relationship” was proven, why is ACIP adopting the recommendation to include all six “risks and uncertainties” in the disclosures and risk-benefit discussions with patients for the “seasonal boosters” when not all updated COVID-19 vaccines are mRNA vaccines, and to my knowledge, no evidence was presented at the ACIP meeting or by the COVID-19 Vaccine Work Group that any or all of these risks and uncertainties apply to the protein subunit vaccine (Novavax)?

As far as the risk or uncertainty included that there can be persistence of spike protein and lipid nanoparticles following vaccination, the manufacturers testified that their studies showed and the FDA reviewed and approved that the spike protein did not persist more than 2 weeks. Where we have seen persistence is in cases of Long COVID following infection. Dr. Drew Weissman, a co-recipient of the 2023 Nobel Prize in physiology or medicine for his discoveries related to the development of the mRNA-based COVID-19 vaccines explained why the Work Group got this wrong to a Stat News reporter. According to Weissman, the mRNA from the vaccine is gone in days. It doesn’t go to the brain or the eyes. “What those studies did is they put huge doses of RNA into a mouse and used very sensitive assays, and that’s where it went.” Instead, if you give the mouse a vaccine equivalent dose, “you see it in the muscle, you see it in the draining lymph node, and that’s about it.”

The Stat News reporter asked Dr. Weissman, “How sure are you? How sure are you that there is not case of mRNA being distributed more widely in the body?” He responded, “I know it’s not distributed widely. I mean, we showed that back in 2017 at vaccine doses. We’ve looked at mice, we’ve looked at macaques, we’ve looked at rabbits, and we’ve done as much as we could on humans at a vaccine dose. You don’t see RNA circulating in the placenta, in the testes, in the heart, in the eye, in the brain, all the places that they list. We and many others have looked and we just don’t see it.”

“And the mRNA could not be persistent? Could one dose of mRNA continue to make spike protein for months in a rare patient?” Answer: “It is absolutely impossible. MRNA is degraded incredibly rapidly. When you modify it, it’s a little slower. It’ll last 24 hours. It never, ever lasts six months. That’s just impossible.”

Finally, let me address the claim that “the safety and efficacy of COVID-19 vaccine during pregnancy have never been tested in appropriate randomized clinical trials. In one randomized trial, there was observed numerical imbalance of a higher number of babies with congenital malformations from vaccinated mothers.” Notice the inherent contradiction: the safety and efficacy in pregnancy has never been tested in a randomized clinical trial. However, in the next sentence, but in one randomized trial (what? I thought there were no randomized trials?) There was in fact a randomized clinical trial, however, that trial was stopped when data became overwhelmingly clear that pregnant women greatly benefitted from COVID-19 vaccination and the study could not ethically continue to have patient abstain from vaccination once its benefit was clear. Now, congenital malformations are scary. Notice the peculiar language used here – “observed numerical imbalance of a higher number.” That is because of two things. First, there was not a statistically significant difference between the two groups, and the rates in the two groups was not statistically different from the background rate of congenital malformations. Second, the overwhelming majority of congenital malformations occur during the first trimester (12 weeks) or pregnancy. None of these women received the vaccine before the 22^nd week of pregnancy. Thus, trying to attribute cause of the malformation to the vaccine doesn’t make any sense.

Vote #4, which was actually the first vote taken is the one that is at least mixed – good and bad, but possibly all good.

It states that the vaccine schedules should be modified to reflect:

• Adults 65 and older – vaccination based upon individual-based decision-making.
• 6 months of age – 64 years – individual-based decision-making with emphasis that the risk-benefit of vaccination is most favorable for individuals at increased risk for severe COVID-19 disease and lowest for those individuals who are not at increased risk.

So, the good news is that this actually expands eligibility for the vaccine far beyond what the Secretary announced on social media. Assuming that the acting Director signs off on this, any child over the age of 6 months and all adults could qualify for the vaccine. Why I stated that it was mixed is that it was my understanding that if the ACIP didn’t actually recommend the vaccine for all these age groups, Medicaid and CHIP, the small and individual health plans, and potentially VFC would not cover the cost of the vaccine. However, the chair of the committee stated that they would be covered under this proposal and the CMS and VFC representatives at the meeting didn’t say otherwise, so if he is right, then this would be fantastic news.

Part II: The Hepatitis B Vaccine (birth dose)

The Issue – Whether the first dose of hepatitis B vaccine (a three-dose series) should continue to be administered in the hospital within 24 hours of delivery to the newborns of mothers who test negative for hepatitis B infection (specifically, when the laboratory returns a negative test on the mother for hepatitis B surface antigen (HBsAg)) or whether the childhood vaccination schedule should be revised to move the date for the first vaccine of the 3-shot series for these children to 1 month.

Why is the vaccine recommendation being revisited?

That was the key question that went largely unanswered. The current recommendation for all newborns to receive their first dose of vaccine within 24 hours of delivery has been in place since 2018. More and more countries around the world are moving towards this practice, and no country that has had a universal (meaning that all newborns are vaccinated regardless of the mother’s hepatitis B infection status) vaccination policy has moved to more selective vaccination as was the proposed motion before the committee. Further, the results of U.S. hepatitis B vaccine policy and practice have led to dramatic reductions in hepatitis B infections and resulting chronic hepatitis B with its various complications (see below) to the point that the U.S. could now consider the possibility of eliminating hepatitis B.

No one suggested that there was new data that showed any concerns over the same data that has been reviewed in the past and for which the current recommendation was based.

Why do we vaccinate newborns?

In 2022, there were 254 million cases of hepatitis B infections in the world, many of which progress to becoming chronic infections that ultimately lead to the development of cirrhosis with the need for liver transplantation to save the person’s life, to hepatocellular cancer (cancer of the liver), and even death. More than $1 billion dollars is spent in the U.S, on hospital care each year for the treatment of hepatitis B related complications. The annual costs of treating a patient with hepatitis B without severe complications ranges from $25,308 to $93,935 and for treating a patient who requires liver transplantation, those annual costs increase to $174,282 to $324,849.

Many people realize that in adults, the major modes of transmission of hepatitis B infection are through intercourse or intravenous drug abuse (it can be transmitted through blood transfusion, but this has become negligible due to screening of blood prior to transfusion), so they don’t understand the need to vaccinate infants given that they would not have either risk factor. It is important to note that half of those who are infected and contagious with hepatitis B do not have symptoms or know that they are infected.

The reason for vaccination of infants in the first 24 hours following birth is related to the fact that infants become infected in much different ways than do adults; in fact, babies become infected from adults. The major risk is a mother transmitting the virus to the infant during the pregnancy or following birth. If no intervention is taken (vaccination of the infant and treatment of the infant with hepatitis B immune globulin), up to 85 percent of infants born to a mother with hepatitis B infection (recall that half of adults don’t realize or know that they are infected) will develop hepatitis B infection. Unfortunately, 90 percent of infants who are infected by their mothers will develop chronic hepatitis B with risk for development of cirrhosis, cancer and/or death (25 percent die from the infection) or the need for liver transplantation.

Another thing that can be difficult for people to understand is then why not just test the mothers for hepatitis B and just vaccinate the children whose mothers test positive. There are lots of reasons why we fail to identify the mothers who are infected. First, as more women have challenges with access to prenatal care, a lot of times, women don’t receive the recommended screening during the early parts of their pregnancy. Second, we are not good at identifying women who are at increased risk for hepatitis B, and while the mother may initially test negative, there are some of these women who will become infected in the interval between the hepatitis test and delivery. Further, women can receive their pregnancy care from a wide range of providers, and screening doesn’t get done in 100 percent of these cases. Also, there are a number of viral hepatitis tests that tell us different things, and sometimes the results may not be understood correctly, transcribed correctly or communicated correctly resulting in the infant not being vaccinated based on this misunderstanding even though the mother is infected. This has led to some recommending that we just test women at the time of delivery. That can address some of these challenges, but not necessarily all. One factor is that these days, if the birth is a normal, uncomplicated vaginal delivery, the patient could end up being admitted and discharged before the hepatitis test result is ready, especially at rural, critical access, and small hospitals that may not be able to run these tests 24 hours a day.

So, the reality is that we end up with about 12 – 16 percent of pregnant mothers not getting the screening hepatitis B test.

Thus, the three-dose series has been recommended to be given within 24 hours of delivery (“the birth dose”), at 1 – 2 months of age, and at 6 – 15 months of age. The protection from hepatitis B infection in the child increases with each dose (protective antibodies in ~25 percent of infants following dose #1, ~ 63 percent of infants after dose #2, and ~95 percent of infants after dose #3 (it is 98 percent if the infant was born healthy and at full term)). Further, while up to about 5 percent of infants will develop fever following the first dose, the vaccine has been determined to be very safe (the risk of fever, irritability, redness at the injection site, etc. vs the risks posed by hepatitis B infection) and the durability of the vaccine has been amazing with protection lasting more than 30 years in more than 90 percent of those vaccinated, with the likelihood of life-long protection.

If perinatal (around the time of birth) exposure from an infected mother was the only mode of transmission to the infant, then not vaccinating children whose mothers are negative on testing would make complete sense, so long as we could ensure that all mothers were tested and that we had the correct results in time before hospital discharge. However, household members and others who will be in contact with the infant (nannies, babysitters, extended friends and family, day care workers, etc.) also can pose a risk because the virus can be transmitted through exposure to body fluids (e.g., saliva) and a family member who is also infected with hepatitis B but unaware could have a scrape, cut or other injury in the house, and the virus is known to be able to remain viable on surfaces in the home for as long as 7 days and only a miniscule amount of that blood is necessary to cause infection in the infant. An unvaccinated child living in the same household as an infected member of the family can account for 7 – 11 percent of those children becoming infected.

What was the recommendation put before the committee by the chair to be voted upon?

“The pediatric vaccine schedule should be updated to reflect the following change:

If the mother tests hepatitis B surface antigen (HBsAg) negative:

• The first dose of hepatitis B vaccine is not given until the child is at least one month old.
• Infants may receive a dose of hepatitis B vaccine before 1 month according to individual-based decision-making.” (shared clinical decision-making).

What were the arguments against the recommendation?

1. We already know from experience before the recommendation was changed to universal vaccination (i.e., when only those infants whose mothers tested positive or their hepatitis B status was unknown), that cases were missed, compliance with the three-dose series was decreased and on-time vaccination was decreased.
2. The longer the interval between birth and vaccination in those children who are infected, the worse the outcomes.
3. Changing the recommendation when there is no new evidence of compelling reason to do so will lead to provider confusion and confusion on the part of parents, and potentially erode vaccine trust further.
4. The consequence of the change would be that the Medicaid, the Children’s Health Insurance Program, (CHIP), and individual and small market health plans would no longer pay for the birth dose vaccines in children whose mothers test negative and the Vaccines for Children Program (VFC) (which pays for vaccines for a little over half of all children in the U.S., including the uninsured, American Indians, Alaska natives and the underinsured who receive their care at federally qualified health centers) would no longer pay for the birth dose vaccine unless ACIP specifically voted against VFC aligning their coverage with the new recommendation.

What was the vote?

This is where things got wild, surprising, and nearly devolved into chaos. The votes on the MMRV vs. MMR + V that I wrote about yesterday and the votes on the hepatitis B birth dose were on the agenda for yesterday. However, after a long day with fatigue setting in, the votes were postponed to Friday. The votes on the MMRV vs MMR + V issue were taken and were as I wrote about yesterday. However, when the vote to modify the childhood vaccination schedule passed, it required a vote to be taken to determine whether the VFC should align their coverage with that new recommendation. It was clear that few understood that while CMS automatically changes coverage in accordance with the new recommendation, the committee must vote as to whether VFC should align coverage with the new recommendation. The motion to vote on didn’t explain any of this, and as members were told that a “yes” vote would mean that parents would have to pay for MMRV if they elected that for their child’s first dose in order to reduce the number of shots the child received and a “no” vote would mean that the VFC, but not CMS, would continue to pay for the MMRV vaccine if a parent elected for their child to receive it, almost no one could wrap their heads around it and there was extensive discussion and questions in an effort to try to understand this, with two members ultimately abstaining from the vote just on the basis that they could not understand the implications of their vote. The motion to align VFC coverage with the new recommendation failed on a 1 – 8 – 3 vote, which I took to mean that members realized that they were effectively taking the medical decision-making away from parents, especially parents that could not afford to pay for the MMRV vaccine, and so while their new recommendation was symbolic, they wanted the vaccine to be covered for if those parents still opted for it, but I was wrong.

Once a speech was given and members realized the confusion that was being created for everyone, there was a motion that passed for reconsideration and a new vote took place in which there remained three abstentions, but 8 of the members changed their vote from no to yes.

Now, all of that was just the votes on the MMRV vs MMR + V issue. While the committee did vote unanimously to recommend that all women be tested for hepatitis B infection during pregnancy (this is what is already in place), I braced myself for what I anticipated would be a vote in favor of changing the birth dose of hepatitis B for infants of mothers who test negative to one month. To my surprise, and based in large part on a complete misunderstanding as to how we assess medication and vaccine safety, the committee voted 11- 1 to table the issue.

What is my take?

Had the issue not been tabled, I would have voted against the new recommendation. There was no new data, no new concerns, and no reason offered as to why a change was needed. Changes to the childhood vaccine schedule are disruptive and require a lot of communication and explanation to a massive health infrastructure across the country. When those changes are needed, they should be made. However, tinkering with the schedule, especially when the lack of expertise on the committee was pretty apparent and multiple liaison organizations expressed grave concerns that there is certain to be more children developing chronic hepatitis B infections is not only deeply concerning, but inconsistent with the supposed MAHA agenda. Unlike many of the vaccine-preventable illnesses, I have seen plenty of cases of chronic hepatitis B disease and I understand its ravages to the human body. It is always difficult to care for patients with severe diseases that threaten their lives; it is a 100-times worse when the disease could have been easily prevented.

Nevertheless, I remain extremely concerned about the potential for ACIP to revisit and alter this well-established universal hepatitis B vaccine recommendation at some point in the future. Today’s decision avoids, at least temporarily, interruptions toward the elimination of this horrible disease in the U.S. 

The success of the hepatitis B vaccine is backed by 40 years of evidence. With 1 billion doses administered globally, and a reduction of 99% in acute infections in children 19 and younger in the U.S., the benefits of the vaccine are irrefutable. Weakening the birth dose recommendation would risk reversing decades of progress and undermines public confidence in a vaccine that prevents a leading cause of liver cancer. 

I indicated above that the question as to why the birth dose was being revisited was “largely” unanswered. I qualified that because on the second day, and my personal guess is that it was related to all the consternation this issue raised from the public health and medical communities, one committee member (Dr. Malone) offered a “reason” indicating that it was incumbent upon the newly constituted committee to revisit these matters to restore the public’s trust. In fact, he went so far as to suggest that the very question being raised by many of the liaison groups was disingenuous, which I find extremely disingenuous in itself given that I don’t believe that Dr. Malone has been the most prominent, influential, and effective purveyor of COVID-19 vaccine disinformation, but he would certainly be on my top 10 list. I find it ironic when those who are setting fires to houses are the ones alleging that the police need to get the arsons under control.