When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV.

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

Background: The variation in the reported vaccine safety and effectiveness could contribute to the high rates of vaccine hesitancy among the general population and healthcare workers in areas where monkeypox (mpox) is circulating. In this review, our objective was to evaluate the safety, immunogenicity, effectiveness, and efficacy of the mpox vaccines. Methods: An extensive search for articles across multiple databases was performed, including searching six databases (PubMed Central, PubMed Medline, Scopus, Web of Science, Cochrane, ProQuest), two pre-print databases (European PMC Preprint and MedRxiv), and Google Scholar. Results: A total of 4290 citations were retrieved from the included databases. Following the removal of duplicates and the initial screening of records, a total of 36 studies were included into the analysis. Additionally, we identified five more studies through manual searches, resulting in a total of 41 eligible articles for qualitative synthesis. The study findings revealed that mpox vaccines demonstrate the ability to generate adequate antibodies; however, their effectiveness may decrease over time, exhibiting varying safety profiles. Most of the included studies consistently reported substantial levels of effectiveness and efficacy against mpox. Interestingly, the number of vaccine doses administered was found to influence the degree of immunogenicity, subsequently impacting the overall effectiveness and efficacy of the vaccines. Furthermore, we found that smallpox vaccines exhibited a form of cross-protection against mpox. Conclusions: Vaccines can be used to prevent mpox and effectively control its spread.

Systematic Review on the Efficacy, Effectiveness, Safety, and Immunogenicity of Monkeypox Vaccine

Introduction During the 2022 mpox outbreak, the province of Quebec, Canada prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (e.g. clinical record of sexually transmitted infections), or supplemented by self-reported risk factor information (e.g. sexual contacts). Methods We conducted a test-negative case-control study between June 19 and September 24, 2022. Information from administrative databases was supplemented by a questionnaire collecting self-reported risk factors specific to the three-week period before testing. Two study populations were assessed: all within the administrative databases (All-Admin) and the subset completing the questionnaire (Sub-Quest). Logistic regression models were adjusted for age, calendar-time and exposure-risk, the latter based on administrative indicators only (All-Admin and Sub-Quest populations) or supplemented by questionnaire information (Sub-Quest population). Results There were 532 All-Admin participants, of which 199 (37%) belonged to Sub-Quest. With exposure-risk adjustment based only on administrative indicators, single-dose mpox VE among All-Admin and Sub-Quest populations was similar at 35% (95%CI:-2-59) and 30% (95%CI:-38-64), respectively. With adjustment supplemented by questionnaire information, Sub-Quest VE increased to 65% (95%CI:1-87). Protection against severe outcomes was higher (VE=82%; 95%CI:-50-98) but with overlapping confidence intervals. Conclusions One vaccine dose reduced mpox risk by about two-thirds when adjustment incorporated self-reported risk factors, but by only one-third when adjustment relied solely upon administrative indicators. Inadequate adjustment for exposure risk may substantially under-estimate mpox VE.

Single-dose effectiveness of mpox vaccine in Quebec, Canada: test-negative design with and without adjustment for self-reported exposure risk

Current SARS-CoV-2 vaccines have demonstrated robust induction of neutralizing antibodies and CD4+ T cell activation, however CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurposed our DNA origami vaccine platform, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific HR2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naïve mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular immune responses in human cells. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities. The programmability of this platform underscores its potential utility in addressing future pandemics.

DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases

Progress in the evaluation of modified vaccinia Ankara vaccine against mpox.

Background Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate its immunogenicity and inform vaccine administration and design. Methods We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and 4/6 convalescent sera were reactive to native mpox proteins. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation: JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells.

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Mpox vaccine and infection-driven human immune signatures

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Mpox vaccine and infection-driven human immune signatures