Smallpox vaccination campaigns resulted in age-associated population cross-immunity against monkeypox virus.

Increased human-to-human transmission of monkeypox virus (MPXV) is cause for concern, and antibodies directed against vaccinia virus (VACV) are known to confer cross-protection against Mpox. We used 430 serum samples derived from the Scottish patient population to investigate antibody-mediated cross-neutralization against MPXV. By combining electrochemiluminescence immunoassays with live-virus neutralization assays, we show that people born when smallpox vaccination was routinely offered in the United Kingdom have increased levels of antibodies that cross-neutralize MPXV. Our results suggest that age is a risk factor of Mpox infection, and people born after 1971 are at higher risk of infection upon exposure.

Evaluation of monkeypox- and vaccinia-virus neutralizing antibodies before and after smallpox vaccination: A sero-epidemiological study.

Since May 2022, several countries outside of Africa experienced multiple clusters of monkeypox virus (MPXV)-associated disease. In the present study, anti-MPXV and anti-vaccinia virus (VACV) neutralizing antibody responses were evaluated in two cohorts of subjects from the general Italian population (one half born before the WHO-recommended end of smallpox vaccination in 1980, the other half born after). Higher titers (either against MPXV or VACV) were observed in the cohort of individuals born before the interruption of VACV vaccination. An association between VACV and MPXV antibody levels was observed, suggesting that the smallpox vaccination may confer some degree of cross-protection against MPXV infection. Results from this study highlight low levels of immunity toward the assessed Orthopoxviruses, especially in young adults, advocating the introduction of a VACV- or MPXV-specific vaccine in case of resurgence of monkeypox disease outbreaks.

Designing a smallpox B-cell and T-cell multi-epitope subunit vaccine using a comprehensive immunoinformatics approach.

Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body. IMPORTANCE: In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.

Predicting vaccine effectiveness for mpox.

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.

Biology of Variola Virus.

Variola virus is an anthroponotic agent that belongs to the orthopoxvirus family. It is an etiological agent of smallpox, an ancient disease that caused massive mortality of human populations. Twentieth century has witnessed the death of about 300 million people due to the unavailability of an effective vaccine. Early detection is the primary strategy to prevent an outbreak of smallpox. Variola virus forms the characteristic pus-filled pustules and centrifugal rash distribution in the infected patients while transmission occurs mainly through respiratory droplets during the early stage of infection. No antiviral drugs are approved for variola virus till date. Generation of first-generation vaccines helped in the eradication of smallpox which was declared by the World Health Organization.

Poxvirus Vaccines: Past, Present, and Future.

Smallpox was a significant cause of mortality for over three thousand years, amounting to 10% of deaths yearly. Edward Jenner discovered smallpox vaccination in 1796, which rapidly became a smallpox infection preventive practice throughout the world and eradicated smallpox infection by 1980. After smallpox eradication, monkeypox vaccines have been used primarily in research and in outbreaks in Africa, where the disease is endemic. In the present, the vaccines are being used for people who work with animals or in high-risk areas, as well as for healthcare workers treating patients with monkeypox. Among all orthopoxviruses (OPXV), monkeypox viral (MPXV) infection occurs mainly in cynomolgus monkeys, natural reservoirs, and occasionally causes severe multi-organ infection in humans, who were the incidental hosts. The first case of the present epidemic of MXPV was identified on May 7, 2022, and rapidly increased the number of cases. In this regard, the WHO declared the outbreak, an international public health emergency on July 23, 2022. The first monkeypox vaccine was developed in the 1960s by the US Army and was based on the vaccinia virus, which is also used in smallpox vaccines. In recent years, newer monkeypox vaccines have been developed based on other viruses such as Modified Vaccinia Ankara (MVA). These newer vaccines are safer and can provide longer-lasting immunity with fewer side effects. For the future, there is ongoing research to improve the current vaccines and to develop new ones. One notable advance has been the development of a recombinant vaccine that uses a genetically modified vaccinia virus to express monkeypox antigens. This vaccine has shown promising results in pre-clinical trials and is currently undergoing further testing in clinical trials. Another recent development has been the use of a DNA vaccine, which delivers genetic material encoding monkeypox antigens directly into cells. This type of vaccine has shown effectiveness in animal studies and is also undergoing clinical testing in humans. Overall, these recent advances in monkeypox vaccine development hold promise for protecting individuals against this potentially serious disease.

Treatment and Vaccination for Smallpox and Monkeypox.

The smallpox infection with the variola virus was one of the most fatal disorders until a global eradication was initiated in the twentieth century. The last cases were reported in Somalia 1977 and as a laboratory infection in the UK 1978; in 1980, the World Health Organization (WHO) declared smallpox for extinct. The smallpox virus with its very high transmissibility and mortality is still a major biothreat, because the vaccination against smallpox was stopped globally in the 1980s. For this reason, new antivirals (cidofovir, brincidofovir, and tecovirimat) and new vaccines (ACAM2000, LC16m8 and Modified Vaccine Ankara MVA) were developed. For passive immunization, vaccinia immune globulin intravenous (VIGIV) is available. Due to the relationships between orthopox viruses such as vaccinia, variola, mpox (monkeypox), cowpox, and horsepox, the vaccines (LC16m8 and MVA) and antivirals (brincidofovir and tecovirimat) could also be used in the mpox outbreak with positive preliminary data. As mutations can result in drug resistance against cidofovir or tecovirimat, there is need for further research. Further antivirals (NIOCH-14 and ST-357) and vaccines (VACΔ6 and TNX-801) are being developed in Russia and the USA. In conclusion, further research for treatment and prevention of orthopox infections is needed and is already in progress. After a brief introduction, this chapter presents the smallpox and mpox disease and thereafter full overviews on antiviral treatment and vaccination including the passive immunization with vaccinia immunoglobulins.

Current Status of Vaccine Development for Monkeypox Virus.

Monkeypox virus (MPXV) of poxviridae family causes a zoonotic disease called monkeypox (Mpox). MPXV cases have a fatality ratio ranging from 0 to 11% globally and have been more prevalent in children. There are three generations of smallpox vaccines that protect against MPXV. First and second generation of the vaccinia virus (VACV) vaccine protects MPXV. However, various adverse side effects were associated with the first and second generations of vaccines. In contrast, the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) replication-incompetent vaccine shows fewer adverse effects and a significant amount of neutralizing antibodies in mammalian cells. A third-generation Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) was approved to prevent Mpox in 2019. Recently, MVA-BN-based Imvanex, Imvamune, and JYNNEOS vaccines have also been administered against MPXV. Globally, the World Health Organization (WHO) declared a global health emergency in May 2022 due to increased MPXV cases. Various computational studies have also designed a multi-epitope-based vaccine against the MPXV. In the multi-epitope-based vaccine, different epitopes like B-cell, Cytotoxic T Lymphocyte (CTL), CD8+, and CD4+ epitopes were derived from MPXV proteins. Further, these epitopes were linked with the help of various linkers to design a multi-epitope vaccine against MPXV. In summary, we have provided an overview of the current status of the vaccine against MPXV.

A Multi-pronged Approach to Addressing Global Poxviruses Vaccine Inequity: A Case of Monkeypox.

Monkeypox has been endemic in Congo and Nigeria for at least five decades. Since early May 2022, there have been numerous unprecedented outbreaks throughout the world in places without any previously reported cases. While a majority of the diagnosed cases have been within Europe and the Americas, several cases have occurred in non-endemic African countries. As of December 2022, 82,999 cases had been reported globally, prompting concern among the World Health Organization (WHO) members. While the WHO has not labeled this epidemic a Global Health Emergency, member states have begun to put forward plans to consolidate their emergency vaccine stockpiles and share the limited number of vaccines made by the single FDA-approved manufacturer, Bavarian Nordic. Many countries are concerned about how vaccines will be shared. Some of the larger donor States are positioned to be the biggest beneficiaries of vaccine sharing, while States from areas that have been suffering from the virus since the 1970s have not been allocated any. This pattern of vaccine distribution echoes that seen during the early part of the COVID-19 pandemic. Due to the similarities between Monkeypox and Smallpox, contact precautions and vaccination seem to be effective strategies to combat its rapid spread. We aim to evaluate how an eradication program model similar to that used for Smallpox can be applied to Monkeypox, and whether it can address vaccine inequity. To do this, we use a multi-pronged approach targeting disease surveillance, vaccine awareness, manufacturing, cost, and distribution strategies.

Introduction of the smallpox vaccine in Napoleonic France, as recorded in contemporary medals.

The smallpox vaccine developed by Jenner in 1798 was successfully introduced in France in 1800 with the support of Napoleon Bonaparte. The medals and tokens (coin-like medals) issued to encourage early-day vaccination activities are described in the context of the changing political situation in that country. In 1800 a private society of subscribers, led by the Duke of La Rochefoucauld-Liancourt was created, along with a Vaccine Committee charged with evaluating the safety and efficacy of vaccination before deciding if vaccination should be extended to the entire population. The Vaccine Committee published a positive report in 1803, and in 1804, the Ministry of the Interior established the "Society for the extinction of smallpox in France by means of the propagation of the vaccine". The creation of the Society made smallpox vaccination an official activity of the empire, facilitating collaboration between government agencies. The vaccine institution, established by Napoleon in 1804, continued its functions until 1820 when the Royal Academy of Medicine was created and took over those functions. This case exemplifies the collaboration that was needed between science and politics to rapidly bring the recently developed smallpox vaccine to the needed population.

Levels of antibodies against the monkeypox virus compared by HIV status and historical smallpox vaccinations: a serological study.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

The 5 C model and Mpox vaccination behavior in Germany: a cross-sectional survey.

BACKGROUND: Due to the authorization of the Mpox vaccines, we aimed to identify determinants of the intention to get vaccinated, actively trying to receive vaccination, and for successfully receiving a vaccination in Germany employing the 5 C model of vaccination readiness. METHODS: Data stem from a cross-sectional online survey that was available online from August 13, 2022 to August 31, 2022. To assess the influence of the 5 C Model on vaccination behavior, we conducted a multinomial logistic regression. RESULTS: 3,338 participants responded to the survey, with 487 already vaccinated and 2,066 intending to receive a vaccination. Confidence and collective responsibility were positively associated with intention to get vaccinated, while complacency was negatively correlated. A higher score on the calculation scale increased the odds of intention to receive vaccination but not with actively having tried to receive a vaccination. Fewer perceived constraints were associated with higher odds to be vaccinated. Patients in practices that focus on HIV treatment were more likely to intend to get vaccinated, to have tried to get vaccinated and to be vaccinated, regardless of indication. While level of education had no impact, having an indication to get vaccinated was a strong predictor of vaccination behavior in all groups. CONCLUSION: Future vaccination campaigns should aim to reduce specific constraints of the target group and make vaccines widely available in primary care institutions beyond HIV-focused practices.

Antibodies Induced by Smallpox Vaccination after at Least 45 Years Cross-React with and In Vitro Neutralize Mpox Virus: A Role for Polyclonal B Cell Activation?

AIMS: To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory. METHODS: Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry. RESULTS: None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals. CONCLUSIONS: ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.

An overview on mRNA-based vaccines to prevent monkeypox infection.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Behavioral Intention of Receiving Monkeypox Vaccination and Undergoing Monkeypox Testing and the Associated Factors Among Young Men Who Have Sex With Men in China: Large Cross-Sectional Study.

BACKGROUND: The worldwide human monkeypox (mpox) outbreak in 2022 mainly affected men who have sex with men (MSM). In China, young men who have sex with men (YMSM) were at a potential high risk of mpox infection due to their sexual activeness and the eased COVID-19 restrictions at the end of 2022. OBJECTIVE: This study aimed to investigate the behavioral intention of receiving mpox vaccination and undergoing mpox testing in 4 different scenarios and explore their associations with background and behavioral theory-related factors among Chinese YMSM. METHODS: An online cross-sectional survey was conducted among YMSM aged 18-29 years from 6 representative provinces of China in September 2022. Participants recruited (recruitment rate=2918/4342, 67.2%) were asked to self-administer an anonymous questionnaire designed based on prior knowledge about mpox and classic health behavior theories. Data on the participants' background, mpox knowledge and cognition, mpox vaccination and testing cognition, and the behavioral intention of receiving mpox vaccination and undergoing mpox testing were collected. Descriptive analysis and univariate and multivariate linear regressions were performed. Geodetector was used to measure the stratified heterogeneity of behavioral intention. RESULTS: A total of 2493 YMSM with a mean age of 24.6 (SD 2.9) years were included. The prevalence of having a behavioral intention of receiving mpox vaccination ranged from 66.2% to 88.4% by scenario, varying in epidemic status and cost. The prevalence of having an mpox testing intention was above 90% in all scenarios regardless of the presence of symptoms and the cost. The positive factors related to vaccination intention included mpox knowledge (ba=0.060, 95% CI 0.016-0.103), perceived susceptibility of mpox (ba=0.091, 95% CI 0.035-0.146), perceived severity of mpox (ba=0.230, 95% CI 0.164-0.296), emotional distress caused by mpox (ba=0.270, 95% CI 0.160-0.380), perceived benefits of mpox vaccination (ba=0.455, 95% CI 0.411-0.498), self-efficacy of mpox vaccination (ba=0.586, 95% CI 0.504-0.668), and having 1 male sex partner (ba=0.452, 95% CI 0.098-0.806), while the negative factor was perceived barriers to vaccination (ba=-0.056, 95% CI -0.090 to -0.022). The positive factors related to testing intention were perceived severity of mpox (ba=0.283, 95% CI 0.241-0.325), perceived benefits of mpox testing (ba=0.679, 95% CI 0.636-0.721), self-efficacy of mpox testing (ba=0.195, 95% CI 0.146-0.245), having 1 male sex partner (ba=0.290, 95% CI 0.070-0.510), and having in-person gatherings with MSM (ba=0.219, 95% CI 0.072-0.366), while the negative factor was emotional distress caused by mpox (ba=-0.069, 95% CI -0.137 to -0.001). CONCLUSIONS: Among Chinese YMSM, the intention of undergoing mpox testing is optimal, while the mpox vaccination intention has room for improvement. A future national response should raise YMSM's mpox knowledge, disseminate updated information about mpox and preventive measures, improve preventive service accessibility and privacy, and provide advice on positively coping with the associated emotional distress.

Influences of mpox disease perceptions, sources and contents of information exposure on mpox vaccine uptake among gay, bisexual, and other men who have sex with men in Hong Kong, China.

BACKGROUND: Following the global mpox outbreak in 2022, multiple regions in Asia have been reporting ongoing mpox cases within high-risk groups, including gay, bisexual, and other men who have sex with men (GBMSM). An optimal level of vaccination rate is essential to prevent further mpox outbreaks. However, no existing studies have examined mpox vaccine uptake among GBMSM in East Asia. METHODS: A cross-sectional survey was conducted among a sample of 531 GBMSM in Hong Kong, China, between March and October 2023. The study used multivariable logistic regression models to investigate the associations between mpox-related disease perceptions, exposures to sources and contents of mpox-related information, and mpox vaccine uptake. RESULTS: The prevalence of mpox vaccine uptake among GBMSM in Hong Kong was 21.7%, with 7.7% completing one dose and 13.9% completing two doses. GBMSM who were younger or earning less monthly income were less likely to have been vaccinated. After adjusting for confounding variables, participants who perceived more negative impacts on their lives if they were to contract mpox, more severe symptoms, and a more coherent understanding of mpox were positively associated with mpox vaccine uptake. In addition, more frequent exposure to information through the following sources: TV, newspaper, radio and posters, government websites, news websites or apps, other people's social media, and communication over the phone or face-to-face was positively associated with mpox vaccine uptake. Finally, more frequent exposure to the following information contents: mpox statistics from other countries, the Hong Kong government's responses to mpox cases, negative information about patients with mpox, and information on prevention and treatment of mpox were positively associated with mpox vaccine uptake. CONCLUSIONS: This study provides timely and evidence-based implications to address health communication and messaging needs in promoting mpox vaccination among GBMSM in Hong Kong, relevant to regions with similar sociocultural contexts.

Breakthrough cases of mpox: One-dose vaccination is associated with milder clinical manifestations.

BACKGROUND: Very few studies have investigated the effectiveness of vaccination in decreasing the severity of breakthrough mpox. Our goal was to estimate the strength of the associations between recent mpox vaccination with MVA-BN and various clinical manifestations of the disease. METHODS: Telephone interviews using standardized questionnaires, upon notification and 28 days later, of the 403 persons with mpox reported to Montreal Public Health in 2022. MVA-BN vaccination data were obtained from the provincial immunization registry. The main outcomes were numbers of skin lesions and body sites affected, other clinical manifestations (OCM) compatible with mpox, complications, and hospitalization. FINDINGS: 155 persons with mpox (39% of 403) had received 1 dose of vaccine at least 14 days before symptom onset. One-dose vaccination, adjusting for age and HIV status, was significantly associated with fewer lesions, sites affected with lesions, and OCMs. HIV-positive persons with breakthrough mpox reported significantly more lesions, sites affected, and OCMs at initial interview, than HIV-negative ones. However, vaccination was associated with a lower risk of all outcomes to the same degree irrespective of HIV status. INTERPRETATION: One dose of MVA-BN vaccine was about 60% effective in decreasing the frequency and extent of clinical manifestations, among both HIV-positive and HIV-negative persons with breakthrough mpox. Beyond preventing infection, mpox vaccination can be promoted to reduce clinical manifestations in persons at risk for mpox, even if HIV+ . FUNDING: This work used data obtained as part of Montreal Public Health's 2022 mpox outbreak response and received no external funding.