We saw an unprecedented global outbreak of the monkeypox virus clade IIb in 2022 that was eventually contained to some degree with education and vaccination of those at highest risk for infection, which for the most part appeared to be men who have sex with multiple male partners.
Most recently, a new outbreak of monkeypox virus clade Ib is happening in African countries that have never had clade I infections, which appear to be transmitted both by close contact and through heterosexual sexual contact. Clade Ia has been known to have a case fatality rate of three to ten times that of Clade IIa infections, but there is little doubt that the lack of health care access and infrastructure in Africa contributes to a higher mortality rate than would be expected in more developed countries. Further, both Clade Ia and Ib infections appear to be far more frequently occurring in children who can suffer higher mortality rates.
The outbreak was declared a public health emergency for the African continent by the African CDC, and then shortly thereafter, was declared a Public Health Emergency of International Concern (PHEIC) by WHO. Almost immediately thereafter, a small number of cases of Clade Ib cases were detected in other countries where citizens had traveled to Africa.
At long last, vaccines are beginning to be delivered to Africa, however, the amounts are far less than that required to vaccinate a sufficient part of the population to ensure that we can bring the outbreak under control and prevent more cases from appearing in countries throughout the world.
One strategy used in combating the Clade IIb outbreak was to administer the vaccine intradermally (immediately under the skin) at 20 percent of the usual dose given subcutaneously (a short needle that goes beyond the skin but stops short of the muscle). This method would then allow a single dose of vaccine delivered in the typical subcutaneous fashion to be stretched out to five doses by using the intradermal route. If this strategy generates the same or better immune response, it would allow us to vaccinate many more of those in Africa giving us a better chance of containing the spread of Mpox, especially since the normal vaccination schedule calls for a second dose to be administered one month later.
A paper entitled: “Reactogenicity and immunogenicity against MPXV of the intradermal administration of Modified Vaccinia Ankara compared to the standard subcutaneous route” was published as a preprint just several days ago Reactogenicity and immunogenicity against MPXV of the intradermal administration of Modified Vaccinia Ankara compared to the standard subcutaneous route | medRxiv, and offers us important insights. This study compared the reactogenicity (local and systemic reactions from the vaccine administration) and immunogenicity (strength of the immune response generated by the vaccine) between these two doses and routes of administration when this vaccine strategy was used in 2022 in Rome.
It was discovered that the intradermal route actually generated slightly higher levels of IgG specific (to monkeypox) antibodies, as well as slightly higher neutralizing antibodies (recall that neutralizing antibodies are those that bind to the virus and interfere with the virus’ ability to infect and enter a cell. You may recall from my prior blog posts that the antibody response is part of our humoral immune response. It certainly appeared that the lower dose given intradermally stimulated an equally, or slightly better, humoral immune response.
However, we had little data as to the effect of these different doses and routes of administration on the cellular immune response. Antibodies cannot enter cells, so their effectiveness is primarily directed at preventing virus from infecting cells. However, once cells are infected, it is the cellular immune response that is primarily directed at killing infected cells, and thereby killing the virus that has infected the cells, and at clearing the virus from the body to eliminate persistence of infection.
The wonderful news from this study was that the cellular immune response was equally stimulated by either route of administration, even considering the reduced dose with the intradermal route.
Finally, not surprisingly, the intradermal route was more reactogenic, however, both routes of vaccine administration were well tolerated by vaccine recipients.
With these findings, I hope that the African CDC, WHO and other groups who are assisting with the vaccine roll-out in Africa will authorize and utilize the intradermal, dose-sparing method so that we can vaccinate a much larger number of people quickly, though of course this study was conducted on Clade IIb virus and we cannot be sure the same results would be attained with Clade Ib, but there is reason to be optimistic, even while those studies are done to confirm. The downside is that intradermal administration is technically more difficult, but generally, most people can be taught the proper technique and don’t require too much experience to become proficient at it.
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