A new retrospective cohort study published in The Lancet Primary Care has provided compelling real-world evidence that the MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) vaccine continues to offer substantial protection against severe monkeypox (mpox) disease more than 1.5 years after immunization. The commentary accompanying the study—written by infectious disease experts Dr. Emily Evans and Dr. Boghuma Titanji of Emory University—highlights how the findings mark a significant step forward in understanding vaccine durability and clinical protection in the face of waning antibody levels.
The original research, conducted in New South Wales (NSW), Australia, by Latham et al., represents the largest and most detailed clinical study to date on breakthrough mpox infections in fully vaccinated individuals. It is particularly significant given the limited baseline immunity in the Australian population due to the absence of historical smallpox vaccination campaigns, a contrast to settings in Europe, North America, and parts of Africa.
Durable Protection Despite Waning Antibodies
The study included 674 confirmed mpox cases between June and November 2024, during Australia’s largest recorded mpox outbreak. Of those, 251 individuals (37%) were fully vaccinated with two doses of MVA-BN. The median interval between the second dose and symptom onset was nearly 22 months.
Key outcomes demonstrate that full vaccination was associated with:
- 89% reduced risk of hospitalization compared to unvaccinated individuals (RR 0.11; 95% CI 0.03–0.43),
- 55% reduction in risk of systemic symptoms like fever, headache, and muscle pain (RR 0.72),
- Significant reduction in extragenital lesions, a potential driver of casual-contact transmission (RR 0.45).
Interestingly, fully vaccinated individuals were slightly more likely to present with anogenital lesions, though these were generally mild and did not lead to hospitalization.
Despite laboratory evidence that antibody titers wane within 5–7 months of vaccination, these clinical findings suggest meaningful protection persists well beyond serological decline. This divergence between antibody kinetics and real-world outcomes adds nuance to the discussion around correlates of protection and vaccine-induced immunity.
Implications for HIV-Positive Individuals
While the Australian cohort included people living with HIV, the study did not stratify clinical outcomes by HIV status. This is a notable omission, given that HIV-positive individuals—especially those with advanced disease—are at substantially higher risk of severe mpox, including disseminated and even fatal outcomes.
Previous research has shown that while people with HIV can mount adequate immune responses to MVA-BN, those with lower CD4 counts or poorly managed HIV may have weaker protection. In one clinical trial, antibody titers were significantly higher in people without HIV compared to those with HIV, despite both groups reaching high seropositivity rates.
The absence of outcome data stratified by HIV status represents a critical gap, especially as current mpox outbreaks in sub-Saharan Africa—where HIV prevalence is high—continue to intensify.
A Public Health Opportunity and National Imperative
The findings have important implications for both national and global health security. Infections with mpox, while relatively rare outside high-risk populations, can escalate quickly during outbreaks and impose significant strain on healthcare systems.
Preventing hospitalizations and systemic symptoms—especially in younger, unvaccinated populations—is not only a clinical goal but also a matter of public health resilience. In the Australian outbreak, the vast majority of mpox patients were men under 50, underscoring the vulnerability of generations never immunized against smallpox.
As Dr. Titanji and Dr. Evans note, leveraging sexual health clinics as vaccination hubs has proven effective, but disparities in access persist. Populations disconnected from such services may face increased risk during future outbreaks, further emphasizing the need for broader, community-engaged vaccination strategies.
Global Equity and the Next Phase: Boosters?
The NSW study’s implication that protection extends well beyond the initial year is reassuring—but it also raises new questions. Should a third (booster) dose be recommended for specific populations? Should HIV-positive individuals, or those with high behavioral exposure risk, receive tailored vaccine schedules?
The commentary urges global immunization technical advisory groups to incorporate these findings into deliberations about MVA-BN booster strategies. It also reinforces the call for equitable global access to MVA-BN, especially in lower-income settings currently grappling with resurging outbreaks.
Notably, viral sequencing in the Australian outbreak revealed no substantial genetic divergence between viruses infecting vaccinated and unvaccinated individuals. This suggests vaccine escape was not a major factor in breakthrough infections and bolsters confidence in the ongoing relevance of the MVA-BN platform.
Next Steps: Research, Policy:
This evidence base provides a firm foundation for future preparedness—but several priorities remain:
- Stratified clinical studies on vaccine efficacy in immunocompromised populations,
- Longitudinal analyses of immune response durability post-MVA-BN,
- Global coordination on vaccination campaigns in areas with rising case counts and high HIV prevalence,
- Booster dose policy frameworks informed by risk profiling, not just time since vaccination.
As mpox transitions from a global health emergency to an endemic risk, the world must shift from reactive containment to proactive, equitable protection—particularly for communities historically underserved by immunization programs.
Sources and Further Reading
Evans EE, Titanji BK. Protection that lasts? MVA-BN against clade IIb mpox. The Lancet Primary Care, 24 July 2025.
Latham NH, Pett J, Katelaris AL, et al. Clinical features of mpox in fully vaccinated people in New South Wales, Australia: a retrospective cohort study. The Lancet Primary Care, 24 July 2025.
Taha AM, Rodriguez-Morales AJ, Sah R. Mpox breakthrough infections: concerns and actions. The Lancet Infectious Diseases, Nov 2023.
Valentina M, Guiulia M, Eleonora C, et al. Humoral and T-Cell Responses Following MVA-BN Booster Vaccination Against Mpox Virus Clades Ib and IIb, MedRxiv pre-print, 7 July 2025.