A new study published in The Lancet Infectious Diseases reveals significant disparities in the effectiveness of Bavarian Nordic's Jynneos vaccine against mpox infection, particularly among HIV-positive individuals, underscoring critical gaps in protection for vulnerable populations.
The research, conducted at Charité Universitätsmedizin Berlin, found that while one dose of Jynneos (smallpox and mpox vaccine, live, non-replicating) demonstrated an overall 58% effectiveness in preventing mpox infection, its efficacy varied dramatically based on HIV status. The vaccine showed 84% effectiveness in individuals without HIV but only 35% effectiveness in those living with HIV.
This combined prospective and retrospective study recruited more than 6,000 men who have sex with men and transgender people aged 18 years and older, providing crucial real-world data on vaccine performance across different populations.
Mpox Global Impact and Risk Factors
Mpox, a viral illness spread through close contact with infected individuals, contaminated objects, or infected animals, has become a significant global health concern. The ongoing Clade II 2022 mpox outbreak has affected over 100,000 people across 122 countries, according to the US Centers for Disease Control and Prevention (CDC).
While mpox symptoms—including blistering rash, fever, muscle aches, sore throat, and swollen lymph nodes—are typically mild in the general population, immunocompromised patients face substantially higher risks. Those with uncontrolled HIV are particularly vulnerable to severe disease, hospitalization, and death from mpox infection.
The current global landscape includes two distinct outbreaks: the widespread Clade II variant with a greater than 99% survival rate, and the more virulent Clade I outbreak in Central and Eastern Africa, which has caused over 21,000 infections since 2024 and poses a greater threat of severe illness and death, especially among immunocompromised individuals.
Vaccine Effectiveness and Immune Response
The study researchers attribute the reduced effectiveness of Jynneos in HIV-positive patients to diminished T-cell responses following vaccination compared to HIV-negative individuals. This finding emphasizes the critical importance of ensuring that patients with HIV receive the complete two-dose vaccination regimen to maximize protection.
"The immunological data clearly shows why we're seeing this efficacy gap," said one of the study's lead investigators. "HIV-positive individuals simply don't mount the same robust immune response after a single dose, making that second dose absolutely essential for this vulnerable population."
Safety Profile and Reactogenicity
The study also evaluated vaccine safety across more than 3,600 participants who received two doses of Jynneos. Local reactions occurred in 70% of individuals after the first dose and 57% after the second dose. Systemic reactions were reported in 22% of individuals after the first dose and 18% after the second dose, with severe reactions being rare.
Notably, reactogenicity was reduced in individuals with HIV—a finding consistent with the vaccine's lower effectiveness in this population. Local reactions occurred in 62% of HIV-positive individuals after the first dose and 52% after the second dose, compared with 74% and 59%, respectively, in individuals without HIV. Similarly, systemic reactions were reported in 20% of HIV-positive individuals after the first dose and 15% after the second dose, versus 24% and 19%, respectively, in those without HIV.
Limited Prevention Options
The current landscape of mpox prevention remains limited. According to GlobalData, only two other vaccines are approved for mpox prevention besides Jynneos: KM Biologics' mpox LC16m8 vaccine and Emergent BioSolutions' ACAM2000. The LC16m8 vaccine has demonstrated safety and efficacy in people with well-controlled HIV.
The development pipeline includes just three mpox vaccines in clinical trials: the LC16m8 mpox vaccine being investigated by the National University of Colombia, BioNTech's BNT-166a, and Moderna's mRNA-1769. Among these, only the Phase III trial for LC16m8 includes a specific study cohort of individuals with stable HIV infection.
Implications for Public Health Strategy
This new data on Jynneos comes at a critical time as global health authorities continue to battle mpox outbreaks worldwide. The findings highlight the urgent need for targeted approaches to protect HIV-positive individuals, who represent one of the most at-risk populations for severe mpox outcomes.
Public health experts emphasize that these results should inform vaccination strategies, particularly in regions with high HIV prevalence. "We need to prioritize complete vaccination series for HIV-positive individuals and potentially explore additional protective measures for this population," noted a public health official familiar with the study.
The research underscores a significant unmet need for more comprehensive studies on mpox in patients with HIV and the development of more effective vaccination options specifically designed to generate robust immune responses in immunocompromised individuals.
As the global response to mpox continues to evolve, these findings provide valuable guidance for clinicians and public health officials working to protect vulnerable populations from this emerging infectious disease threat.
