RESUMEN
Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.
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Anticuerpos Antivirales , Liofilización , Vacuna contra Viruela , Humanos , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/efectos adversos , Vacuna contra Viruela/administración & dosificación , Femenino , Masculino , Adulto , Adulto Joven , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/efectos adversos , Inmunidad Humoral , Inmunidad Celular , Adolescente , Viruela/prevención & control , Viruela/inmunología , Congelación , Vacunas AtenuadasRESUMEN
Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.
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Vacuna BCG , Cicatriz , Piel , Vacuna contra Viruela , Vacunación , Animales , Humanos , Vacuna BCG/administración & dosificación , Vacuna BCG/inmunología , Cicatriz/etiología , Cicatriz/patología , Cicatriz/inmunología , Piel/patología , Piel/inmunología , Viruela/prevención & control , Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Vacuna contra Viruela/inmunologíaRESUMEN
BACKGROUND: Since July 23, 2022, global mpox cases reached 92,546, with over 31,000 in the United States. Asymptomatic carriage is a critical mechanism influencing the global dissemination of mpox. Seroprevalence studies are crucial for determining the epidemic's true burden, but uncertainties persist in serologic assay performance and how smallpox vaccination may influence assay interpretation. OBJECTIVES: Our study aimed to assess the performance of several diagnostic assays among mpox-positive, vaccinated, and pre-outbreak negative control samples. This investigation sought to enhance our understanding and management of future mpox outbreaks. STUDY DESIGN: Serum samples from 10 mpox-positive, five vaccinated uninfected, and 137 pre-outbreak controls were obtained for serological testing. The mpox-positive samples were obtained around 100 days post symptom onset, and vaccinated patients were sampled approximately 90 days post-vaccination. Multiple diagnostic assays were employed, including four commercial ELISAs (Abbexa, RayBioTech, FineTest, ProteoGenix) and a multiplex assay (MesoScale Diagnostics (MSD)) measuring five mpox and five smallpox antigens. RESULTS: Three commercial ELISA kits had low specificity (<50â¯%). The Proteogenix ELISA targeting the E8L antigen had a 94â¯% sensitivity and 87â¯% specificity. The E8L antigen on the MSD assay exhibited the greatest distinction between exposure groups, with 98â¯% sensitivity and 93â¯% specificity. CONCLUSIONS: None of the assays could distinguish between mpox-positive and vaccinated samples. The MSD assay targeting the MPXV E8L antigen demonstrated the greatest differentiation between mpox-positive and pre-outbreak negative samples. Our findings underscore the imperative to identify sensitive and specific assays to monitor population-level mpox exposure and infection.
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Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad , Humanos , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Masculino , Femenino , Adulto , Mpox/diagnóstico , Estudios Seroepidemiológicos , Pruebas Serológicas/métodos , Persona de Mediana Edad , Adulto Joven , Vacuna contra Viruela/inmunología , Brotes de Enfermedades , Vacunación , Estados Unidos , AdolescenteRESUMEN
A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving "monkeypox virus" and "vaccinations", and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31-0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42-0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22-0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.
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Mpox , Vacuna contra Viruela , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Vacuna contra Viruela/efectos adversos , Humanos , Mpox/prevención & control , Mpox/inmunología , Mpox/epidemiología , Vacunación , Monkeypox virus/inmunología , Viruela/prevención & control , Viruela/inmunología , Eficacia de las Vacunas , Inmunogenicidad Vacunal , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , AnimalesRESUMEN
INTRODUCTION: Before the global mpox outbreak which began in 2022, the real-world vaccine effectiveness (VE) of mpox vaccines was unknown. We quantified the VE in the global population of 3rd generation or later mpox vaccines (MVA-BN, LC16m8, OrthopoxVac) compared with unvaccinated or other vaccinated states for infection, hospitalization and death. VE was stratified by 1-dose and 2-doses and post-exposure prophylaxis (PEP). METHODS: Studies were included if they measured vaccine efficacy or effectiveness in humans. Animal studies and immunogenicity studies were excluded. MEDLINE, Web of Science, Google Scholar, Embase, MedRxiv and grey literature were searched from January 1st, 1970, with the last search run on November 3, 2023 (Prospero, CRD42022345240). Risk of publication bias was assessed via funnel plots and Egger's test, and study quality via Newcastle-Ottawa scales. RESULTS: A total of 11,892 records were identified via primary search, 3,223 via citation chasing. Thirty-three studies were identified of 3rd generation vaccines, 32 of which were MVA-BN. Two additional studies were re-analysis of existing data. Most of these studies were focused on gay, bisexual, or other men who have sex with men between the ages of 18-49 in May to October of 2022. VE of 1 dose of MVA-BN was 76% (95%CI 64-88%) from twelve studies. VE of 2 doses was 82% (95%CI 72-92%) from six studies. VE of MVA-BN PEP against mpox was 20% (95%CI -24-65%) from seven studies. All VE are calculated from random effects estimates. 18/33(55%) studies were rated as poor, 3/33(9%) as fair and 12/33(36%) as good. Studies included in the meta-analysis had higher quality: 11/16 (69%) were rated as good quality. CONCLUSION: Both 1 and 2 doses of MVA-BN are highly effective at preventing mpox. Effectiveness estimates, specifically of PEP are limited by immortal time bias, predominant mode of mpox transmission, and real-world vaccine timing of administration.
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Eficacia de las Vacunas , Humanos , Mpox/prevención & control , Mpox/inmunología , Profilaxis Posexposición/métodos , Vacunación/métodos , Masculino , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificaciónRESUMEN
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.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Monkeypox virus , Vacuna contra Viruela , Vacunación , Virus Vaccinia , Humanos , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Masculino , Adulto , Femenino , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Italia/epidemiología , Monkeypox virus/inmunología , Adulto Joven , Estudios Seroepidemiológicos , Persona de Mediana Edad , Virus Vaccinia/inmunología , Mpox/epidemiología , Mpox/inmunología , Adolescente , Viruela/prevención & control , Viruela/inmunología , Viruela/epidemiología , Protección Cruzada/inmunología , Anciano , Estudios de Cohortes , NiñoRESUMEN
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.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Monkeypox virus , Mpox , Vacuna contra Viruela , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Adulto , Persona de Mediana Edad , Monkeypox virus/inmunología , Adulto Joven , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Mpox/inmunología , Mpox/prevención & control , Femenino , Adolescente , Anciano , Masculino , Protección Cruzada/inmunología , Escocia , Factores de Edad , Pruebas de Neutralización , Niño , Vacunación , Viruela/prevención & control , Viruela/inmunología , Preescolar , Reacciones Cruzadas , Anciano de 80 o más AñosRESUMEN
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.
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Viruela , Virus de la Viruela , Humanos , Virus de la Viruela/patogenicidad , Virus de la Viruela/genética , Virus de la Viruela/fisiología , Viruela/virología , Viruela/prevención & control , Viruela/transmisión , Animales , Vacuna contra Viruela/inmunología , Brotes de Enfermedades/prevención & controlRESUMEN
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.
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Vacuna contra Viruela , Humanos , Animales , Vacuna contra Viruela/inmunología , Viruela/prevención & control , Viruela/inmunología , Viruela/epidemiología , Viruela/historia , Historia del Siglo XXI , Historia del Siglo XX , Mpox/prevención & control , Mpox/epidemiología , Mpox/inmunología , Infecciones por Poxviridae/prevención & control , Infecciones por Poxviridae/inmunología , Infecciones por Poxviridae/epidemiología , Poxviridae/inmunología , Poxviridae/genética , Monkeypox virus/inmunología , Monkeypox virus/genética , Vacunación , Vacunas Virales/inmunología , Desarrollo de VacunasRESUMEN
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.
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Antivirales , Mpox , Vacuna contra Viruela , Viruela , Viruela/prevención & control , Viruela/epidemiología , Viruela/inmunología , Viruela/historia , Humanos , Antivirales/uso terapéutico , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/uso terapéutico , Mpox/epidemiología , Mpox/prevención & control , Mpox/inmunología , Vacunación/métodos , Virus de la Viruela/inmunología , Virus de la Viruela/genética , Animales , Citosina/análogos & derivados , Citosina/uso terapéutico , Monkeypox virus/inmunología , Monkeypox virus/patogenicidad , Monkeypox virus/genética , Inmunización Pasiva/métodos , Organofosfonatos/uso terapéutico , Isoindoles/uso terapéutico , Cidofovir/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Benzamidas , FtalimidasRESUMEN
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.
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Monkeypox virus , Mpox , Vacuna contra Viruela , Desarrollo de Vacunas , Humanos , Mpox/prevención & control , Mpox/inmunología , Animales , Monkeypox virus/inmunología , Monkeypox virus/genética , Vacuna contra Viruela/inmunología , Anticuerpos Neutralizantes/inmunologíaRESUMEN
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.
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Salud Global , Mpox , Humanos , Mpox/epidemiología , Mpox/prevención & control , Mpox/inmunología , Vacuna contra Viruela/inmunología , Monkeypox virus/inmunología , Monkeypox virus/genética , Vacunación , Organización Mundial de la Salud , Disparidades en Atención de SaludRESUMEN
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.
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Vacuna contra Viruela , Eficacia de las Vacunas , Animales , Humanos , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Vacunación/métodos , Vaccinia/inmunología , Vaccinia/prevención & control , Monkeypox virusRESUMEN
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.
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Anticuerpos Antivirales , Infecciones por VIH , Monkeypox virus , Vacuna contra Viruela , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Infecciones por VIH/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Adulto , Femenino , China/epidemiología , Persona de Mediana Edad , Monkeypox virus/inmunología , Viruela/inmunología , Viruela/prevención & control , Viruela/epidemiología , Viruela/historia , Vacunación , Mpox/inmunología , Mpox/epidemiología , Mpox/historia , Reacciones Cruzadas/inmunología , Adulto Joven , Ensayo de Inmunoadsorción Enzimática , Virus Vaccinia/inmunologíaRESUMEN
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.
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Biología Computacional , Epítopos de Linfocito B , Epítopos de Linfocito T , Vacuna contra Viruela , Viruela , Vacunas de Subunidad , Virus de la Viruela , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/química , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/química , Epítopos de Linfocito T/genética , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/química , Vacunas de Subunidad/genética , Humanos , Vacuna contra Viruela/inmunología , Virus de la Viruela/inmunología , Virus de la Viruela/genética , Viruela/prevención & control , Viruela/inmunología , Linfocitos T/inmunología , Linfocitos B/inmunología , Simulación del Acoplamiento Molecular , Péptidos/inmunología , Péptidos/química , InmunoinformáticaRESUMEN
We assessed early antibody responses after two doses of JYNNEOS (IMVANEX) mpox vaccine in the District of Columbia (D.C.) in persons at high risk for mpox without characteristic lesions or rash. Participants with PCR mpox negative specimens (oral swab, blood, and/or rectal swab) on the day of receipt of the first vaccine dose and who provided a baseline (day 0) serum sample and at least one serum sample at â¼28, â¼42-56 days, or 180 days post vaccination were included in this analysis. Orthopoxvirus (OPXV)-specific IgG and IgM ELISAs and neutralizing antibody titers were performed, and longitudinal serologic responses were examined. Based on participants' IgG and IgM antibody levels at baseline, they were categorized as naïve or non-naïve. Linear mixed effects regression models were conducted to determine if IgG antibody response over time varied by age, sex, HIV status, and route of administration for both naïve and non-naïve participants. Among both naïve and non-naïve participants IgG seropositivity rates increased until day 42-56, with 89.4 % of naïve and 92.1 % of non-naïve participants having detectable IgG antibodies. The proportion of naive participants with detectable IgG antibodies declined by day 180 (67.7 %) but remained high among non-naïve participants (94.4 %). Neutralizing antibody titers displayed a similar pattern, increasing initially post vaccination but declining by day 180 among naïve participants. There were no significant serologic response differences by age, sex, or HIV status. Serologic response did vary by route of vaccine administration, with those receiving a combination of intradermal and subcutaneous doses displaying significantly higher IgG values than those receiving both doses intradermally. These analyses provide initial insights into the immunogenicity of a two-dose JYNNEOS PEP regimen in individuals at high risk of mpox exposure in the United States.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina M , Humanos , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Inmunoglobulina G/sangre , Adulto , Anticuerpos Neutralizantes/sangre , Persona de Mediana Edad , Adulto Joven , Inmunoglobulina M/sangre , Vacuna contra Viruela/inmunología , Vacuna contra Viruela/administración & dosificación , Adolescente , Orthopoxvirus/inmunología , Vaccinia/inmunología , Vacunación/métodos , Estudios de CohortesRESUMEN
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.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Linfocitos B , Reacciones Cruzadas , Vacuna contra Viruela , Virus Vaccinia , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Linfocitos B/inmunología , Chlorocebus aethiops , Reacciones Cruzadas/inmunología , Ensayo de Inmunoadsorción Enzimática , Memoria Inmunológica , Activación de Linfocitos , Pruebas de Neutralización , Orthopoxvirus/inmunología , Viruela/inmunología , Viruela/prevención & control , Vacuna contra Viruela/inmunología , Linfocitos T/inmunología , Vacunación , Virus Vaccinia/inmunología , Células Vero , Monkeypox virus/inmunologíaRESUMEN
The mpox outbreak in 2022 launched a vaccination campaign employing an existing vaccine with moderate protection, highlighting the lack of scalable Orthopoxvirus vaccines with optimal protection. In this issue of Cell, Zuiani et al. report pre-clinical findings of an mRNA-based mpox vaccine, paving the way for Phase I/II clinical trials.
Asunto(s)
Vacuna contra Viruela , Vacunas Virales , Vacunas de ARNm , Animales , Monkeypox virus/inmunología , Vacunas de ARNm/inmunología , Primates , Vacuna contra Viruela/inmunología , Vacunas Virales/inmunologíaRESUMEN
BACKGROUND: After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all. RESULTS: We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV). CONCLUSIONS: We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.