#18,305
Not quite a month ago, in EID Journal Dispatch: Mpox Epidemiology and Vaccine Effectiveness, England, 2023, we looked at a report that found that that nearly half of new community acquired mpox cases in 2023 were in vaccinated individuals. The authors wrote:
Nearly half of outbreak case-patients in 2023 were vaccinated, and there were more cases among those who had received 2 doses of MVA-BN vaccine than among those who had received 1 dose.This unexpected result, they suspect, may have more to do with the risk behavior of some who may feel overly `protected' by two-doses of the vaccine, rather than the vaccine itself.
Peak immunity is expected to be reached 14 days after the second dose of JYNNEOS vaccine. The duration of immunity after one or two doses of JYNNEOS is currently unknown.
Last March, in ECCMID 2024 Study: Mpox (monkeypox) Antibodies Wane Within A Year of Vaccination) we looked at a study by researchers from Erasmus MC in Rotterdam that found:
. . . recipients of the 2-Dose JYNNEOS/ IMVANEX/ IMVAMUNE mpox vaccine who did not receive a childhood smallpox vaccination (discontinued in the 1970s) experienced substantial drops in their immune response after 12 months.
Another presentation, released at roughly the same time from Sweden (see Immune response to MPXV wanes rapidly after intradermal vaccination with MVA-BN (Jynneos)) found an even quicker loss (> 28 days) of detectable neutralizing antibodies after the second vaccination, writing:
Our findings corroborate previous data showing that intradermal MVA-BN vaccination results in neutralizing antibodies only in a proportion of vaccinees, and that a significant decline occurs already during the first months post-vaccination. Immunity after MPXV infection mounts a higher and more robust neutralizing response. In conclusion, the findings merits the study of booster doses.
The levels of detectable neutralizing antibodies may not tell the full story when in comes to the duration of vaccine protection - which also includes reducing the severity of illness - but right now it is the best metric we have.
This week we have another study - published in Eurosurveillance, again from researchers at Erasmus MC - which finds orthopoxvirus-specific antibodies were undetectable in many at-risk individuals born after 1974 (when smallpox vaccinations were halted), 12 months after receiving their second dose.
Due to it length, and technical nature, I've only posted some excerpts. Follow the link to read it in its entirety. I'll have a postscript after the break.
Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023
Leanne PM van Leeuwen1,2,* , Marc C Shamier1,* , Babs E Verstrepen1 , Hannelore M Götz3 , Katharina S Schmitz1 , Najlae Akhiyate1 , Koen Wijnans1 , Susanne Bogers1 , Martin E van Royen4 , Eric CM van Gorp1,2 , Marion PG Koopmans1 , Rory D de Vries1,** , Corine H GeurtsvanKessel1,** , Luca M Zaeck1
Little is known about the durability of antibody responses, and the correlation between waning immunity and long-term effectiveness of MVA-BN vaccination.
In this report, we investigated the durability of orthopoxvirus-specific antibody responses and report the longitudinal antibody dynamics up to 418 days after MVA-BN vaccination in two risk groups, namely GBMSM and laboratory workers.(SNIP)Here, we showed that MVA-BN vaccination induced binding and rMVA-GFP-neutralising antibodies in previously unvaccinated at-risk study participants (born in 1974 or later), and that vaccination boosts binding antibody levels in historically vaccinated at-risk individuals (born before 1974). Binding and neutralising antibody levels in non-primed at-risk individuals declined rapidly at 1-year follow-up and became undetectable in a considerable proportion of cases.
Measuring the immunogenicity of MVA-BN is crucial for understanding the impact of immunisation strategies and supporting vaccine effectiveness (VE) studies. We have previously shown that a two-dose MVA-BN vaccination regimen is immunogenic in individuals without pre-existing immunity [8]; vaccination resulted in the production of VACV-specific binding antibodies, rMVA-GFP nAbs, and MPXV nAbs 1 month after the second dose. However, the levels of MPXV nAbs were low compared with those after historic smallpox vaccination or after MPXV infection [8]. In the initial months after the start of MVA-BN vaccination, VE studies yielded an estimated aggregate VE of 82% after two doses [9,10].
However, while antibodies induced by historic smallpox vaccination using first- or second-generation vaccines can be detected for decades [11], we find rapid waning of antibody in vaccine recipients without pre-existing immunity, which aligns with prior studies into the longevity of orthopoxvirus-specific antibodies after MVA-BN vaccination [12-16]. We expand on those by providing longitudinal immunological follow-up of over 1 year in those directly at risk of MPXV infection.
While the clinical significance of low to absent antibody levels 1 year after vaccination remains unclear due to the absence of a clearly defined correlate of protection, waning antibody levels raise the important question whether these individuals are still protected and if this could possibly facilitate mpox resurgence. A recent report suggested that the level of circulating titres might indeed not be the only marker of protection and that other parts of the immune system, including the role of cell-mediated immunity and the robustness of memory responses, might be more important determinants of disease outcome [17].
Combined with the continuing burden of MPXV, this highlights the importance of further investigating the long-term efficacy of MVA-BN. Ongoing circulation of clade I MPXV on the African continent, including the emergence of clade Ib [4], necessitates future studies elaborating on the cross-reactivity of vaccine-induced antibody responses against clade Ia/b MPXV [5]. In addition, administration of a booster dose 1 year after the initial dose could be considered to improve vaccine immunogenicity [8,15].
Conclusion
In this study, we demonstrate a rapid decline in binding and neutralising antibodies 1 year after MVA- N vaccination in non-primed at-risk individuals. Taken together, our data contribute to the understanding of waning humoral immune responses following MVA-BN vaccination and support decision-making on vaccination strategies.
While there has been some discussion of the possible need for booster shots - given the finite supply of the mpox vaccine, and the pressing needs for it in Africa - it is hard to see how both can be accommodated in the near term.
Complicating matters further, last month an NIH Study Found Tecovirimat (TPOXX) Antiviral Did Not Improve Outcomes From Clade I Infection, while another recent study, published in NEJM Evidence, reported a small number of serious adverse events (SAEs) among (mostly immunocompromised) patients receiving the antiviral for clade II infections.Currently, the CDC does not recommend `boosters' for the JYNNEOS vaccine beyond the initial 2-doses, although they continue to review the data.
While the JYNNEOS vaccine (and potentially the TPOXX antiviral) remain important tools in our battle against the Mpox virus, neither are a `silver bullet' against the virus.
And if the vaccine's protection truly wanes after 12 months, that is something that recipients need to be aware of, so they can make informed decisions going forward.
