#18,941
With Mpox clade IIb still spreading globally, and recently joined by a more serious clade Ib (see Los Angeles County Reports 3 (locally acquired) Clade I Mpox Cases in a Week), the CDC currently recommends that those at higher risk (see above) receive 2 doses (4 weeks apart) of the JYNNEOS vaccine.The duration of protection after the 2-dose series is still being studied, but recently published data indicate protection might be >5 years (22). At this time, persons who have been vaccinated with the 2-dose JYNNEOS series do not require an additional dose, nor do they need to be revaccinated during a future outbreak.
Although the 2-dose JYNNEOS series may not be as effective in severely immunocompromised persons, it is not known whether additional doses will improve effectiveness; in addition, some data have suggested that more than 2 doses may cause increased reactogenicity (22) and for this reason, additional doses are not recommended. As more data become available, CDC might provide additional guidance.
At the same time, we've seen a series of studies from around the globe suggesting that the JYNNEOS vaccine's protection may wane rapidly; particularly in those who never received a smallpox vaccination.
Eighteen months ago, 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.
A little over a year ago, in EID Journal Dispatch: Mpox Epidemiology and Vaccine Effectiveness, England, 2023, we saw a study which found that nearly half of new community acquired mpox cases in 2023 were in vaccinated individuals. They note:
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 suspected, may have had more to do with the risk behavior of some who may feel `protected' by two-doses of the vaccine, than the vaccine itself.
And to be fair, it was never expected that the JYNNEOS vaccine would be 100% effective, or that it would convey life-long immunity. The authors also revealed `. . . that no vaccinated persons had been hospitalized for mpox in 2023, indicating that the MVA-BN vaccine probably protects against severe disease requiring hospitalization.'
In November of 2024, in Preprint: The Two-dose MVA-BN Mpox Vaccine Induces a Nondurable and Low Avidity MPXV-specific Antibody Response, we looked at a study by the NYC OSMI Study Group that found - after 5 to 7 months - a waning antibody response in vaccine recipients who were never `primed' with the smallpox vaccine.
Admittedly, antibody levels are just one potential measure of immunity, and may not tell the whole story. Cell-mediated immunity (CMI) and innate immunity may also play critical roles in long-term protection would not correlate directly with antibody levels
The NYC OSMI Study Group is back with another preprint, this time looking at the impact of a 3rd `booster' shot of the JYNNEOS vaccine; which they find improves the duration of protection.
A three-dose MVA-BN mpox vaccination series improves the quality of anti-monkeypox virus immunity
Aaron L. Oom, Kesi K. Wilson, Stephanie Rettig,Michael Tuen, Marie I. Samanovic, Angelica C. Kottkamp, Ramin Sedaghat Herati, Ralf Duerr, Mark J. Mulligan the NYC OSMI Study Group
doi: https://doi.org/10.1101/2025.10.31.25339252
This article is a preprint and has not been peer-reviewed [what does this mean?]
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Abstract
The 2022 global outbreak of clade IIb mpox represented a turning point in public health’s handling of poxviruses. The primary vaccine available for prevention of mpox is modified vaccinia Ankara from Bavarian-Nordic (MVA-BN). We previously reported a nondurable and low avidity antibody response against mpox elicited by MVA-BN.In this study, we expanded upon this knowledge by employing a microneutralization assay to measure monkeypox virus (MPXV) neutralizing titers and a multiplexed immunoassay to assess IgG titers and avidity against eight MPXV antigens and two vaccinia antigens. Through a machine learning analysis, we uncovered that MVA-BN vaccinees without prior smallpox vaccination largely return to a baseline seroprofile within a year of immunization.
Notably, we identified a discrete population within this group that mounted a robust neutralizing antibody response associated with a longer dosing interval during the MVA-BN primary series.
Furthermore, we found that boosting with a third dose of MVA-BN increases IgG avidity against certain MPXV antigens, as part of a booster-specific seroprofile. These findings provide critical insights into optimizing immune responses through MVA-BN boosters, presenting a promising approach to addressing the limited MPXV-specific immunity observed following the primary series.
(SNIP)
Discussion:
Building upon previous work in the field, this study provides critical new insights into the immunological landscape shaped by MVA-BN vaccination. We have demonstrated that 1) the seroprofiles of MVA-BN vaccinees return to an overall baseline state within a year of vaccination, highlighting the transient nature of the induced immunity; 2) low IgG avidity dominates the MVA-BN response; and 3) a longer dosing interval during the primary vaccination series is associated with induction of a transitory “Robust Responder” state characterized by higher peak neutralizing titers. These new results offer crucial updates to existing literature that has demonstrated a poorly durable anti-MPXV response following the MVA-BN primary series
Our findings here also offer further clarity to previous work that demonstrated improved antibody responses following boosting (4,11,25,26). We have shown here that these booster mediated improvements extend to antibody quality in terms of avidity. These results highlight the potential of booster doses to address the insufficient durability of protection provided by the primary series. The addition of a third dose offers an accessible and straightforward strategy for enhancing mpox immunity, particularly in settings where public health officials confirm insufficient protection from the two-dose series.
However, this research adds an important dimension to our understanding of the limitations of non-replicating poxvirus vaccines, as even boosting with a third MVA-BN dose does not fully recreate the seroprofile induced by initial smallpox vaccination with replicating VACV. Further studies are needed to determine what a useful threshold of immunity looks like as it pertains to protection and will inform development of subsequent generations of improved OPXV vaccines.Complicating matters even further, a little over a year ago an NIH Study Found Tecovirimat (TPOXX) Antiviral Did Not Improve Outcomes From Clade I Infection, while another 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.
While the JYNNEOS vaccine (and potentially, still the TPOXX antiviral) remain important tools in our battle against the Mpox virus, neither are a `silver bullet' against orthopoxviruses.
And perhaps most importantly - if the vaccine's protection truly does wane after 8 to 12 months - recipients need to be made aware of that, so they can make informed and safer decisions going forward.
