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.
Asunto(s)
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.
Asunto(s)
Vacuna BCG , Cicatriz , Piel , Vacuna contra Viruela , Vacunación , Humanos , Vacuna BCG/efectos adversos , Vacuna BCG/inmunología , Cicatriz/etiología , Cicatriz/patología , Cicatriz/inmunología , Vacuna contra Viruela/efectos adversos , Vacuna contra Viruela/inmunología , Vacunación/efectos adversos , Piel/patología , Piel/inmunología , Viruela/prevención & control , Viruela/inmunología , AnimalesRESUMEN
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.
Asunto(s)
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
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.
Asunto(s)
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.
Asunto(s)
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
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.
Asunto(s)
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.
Asunto(s)
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
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.
Asunto(s)
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.
Asunto(s)
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
BACKGROUND: After the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV infections after Mpox (formerly monkeypox) occurrences, such as the latest global outbreak in 2022-2023. This study aimed to provide crucial insights for the development of effective public health policy making against mpox in populations residing in regions where the virus is not prevalent. METHODS: This study used enzyme-linked immunosorbent assays (ELISA) to examine smallpox and mpox antibodies in Koreans with three different age groups. We analyzed 56 sera obtained from a tertiary care hospital in South Korea between September 2022 and April 2023. Plasma levels of antibodies against the viral proteins of smallpox (variola cytokine response-modifying protein B) and MPXV (A29) were measured using enzyme-linked immunosorbent assays. RESULTS: Plasma samples from participants in their early 40 s and older exhibited higher reactivity to viral antigens than those from younger participants. Furthermore, there was a strong positive correlation in antibody positivity for the two different viruses across the sera. CONCLUSIONS: The presence of low antibody levels in participants Ë40 years may hinder their ability to defend against OPXV. Therefore, it is imperative to implement effective public health measures to mitigate the transmission of OPXV within the community. These findings serve as fundamental information for devising strategies to combat mpox efficiently, particularly in regions where the virus is not prevalent.
Asunto(s)
Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Orthopoxvirus , Humanos , Adulto , Anticuerpos Antivirales/sangre , República de Corea/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven , Femenino , Orthopoxvirus/inmunología , Factores de Edad , Salud Pública , Anciano , Adolescente , Formación de Anticuerpos , Viruela/prevención & control , Viruela/inmunología , Infecciones por Poxviridae/inmunología , Infecciones por Poxviridae/epidemiología , Mpox/epidemiología , Mpox/inmunologíaRESUMEN
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
Gazeta de Madrid publicó un Suplemento el 14 de octubre de 1806 dando noticia de la llegada y recepción al Director de la Real Expedición Filantrópica de la Vacuna, Francisco Xavier Balmis, por parte del Rey Carlos IV. Había finalizado su periplo dando la vuelta al mundo por los territorios españoles de ultramar, llevando la vacuna contra la viruela brazo a brazo con la ayuda de una cadena humana de niños, creando Juntas de Vacunación e intentando encontrar vacas concowpox. La publicación refrendó las políticas de una monarquía borbónica en decadencia y significó el momento álgido de la carrera profesional de Balmis. Ambas partes ganaban: la Corona publicitándose como financiadora y organizadora del viaje altruista en línea con expediciones científicas anteriores; Balmis pasando a la historia de la Salud Pública como director de la primera campaña internacional de vacunación. No fue el final de la expedición, ya que el resto de los expedicionarios aún seguían vacunando en Filipinas y América del Sur. El objetivo de este estudio fue analizar la importancia de la Gazeta de Madrid como periódico, describir los contenidos de la noticia, verificar el origen de las fuentes documentales que apoyaron su redacción y comprobar el impacto y citas que tuvo a lo largo del siglo XIX en publicaciones en idioma español. Los componentes de la noticia, su proveniencia, así como la participación de Balmis en su redacción han quedado probados. La importancia del Suplemento estribó en su utilidad como recurso para recordar y poner en valor la expedición.(AU)
The Madrid Gazette published a Supplement on October 14, 1806, regarding the arrival of the Director of the Royal Expedition Vaccine Philanthropy, Francisco Xavier Balmis, and the reception held by King Carlos IV. Balmis had completed his journey across the Spanish overseas territories, taking the vaccine against smallpox from arm to arm with the help of a human chain of children. During this journey, Balmis also established Vaccination Boards and endeavoured to identify cows with cowpox. The publication endorsed the policies of a declining Bourbon monarchy and marked the peak of Balmis professional career. Both sides emerged victorious: the Crown showcased itself as the sponsor and organiser of this altruistic journey, in line with prior scientific expeditions; and Balmis secured his place in Public Health history as the director of the first international vaccination campaign. This did not mean the culmination of the expedition, as other members were still administering vaccinations in the Philippines and South America. The main objective of this study was to assess the importance of the newspaper Madrid Gazette, outline the contents of the publication, authenticate the origins of the documentary sources underpinning its composition, and confirm its impact and citations throughout 19 th -century Spanish publications. The components of the publication, its origins, as well as Balmis involvement in its creation, have been substantiated. The Supplements importance is defined by its utility as a resource for commemorating and appreciating the expedition.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Vacunas/historia , Vacunación/historia , Vacuna contra Viruela/historia , Viruela/inmunología , España , Historia del Siglo XIX , Viruela/historia , Viruela/prevención & controlRESUMEN
Background aims: E3L is an immediate-early protein of vaccinia virus (VV) that is detected within 0.5 h of infection, potentially before the many immune evasion genes of vaccinia can exert their protective effects. E3L is highly conserved among orthopoxviruses and hence could provide important protective T-cell epitopes that should be retained in any subunit or attenuated vaccine. We have therefore evaluated the immunogenicity of E3L in healthy VV-vaccinated donors. Methods: Peripheral blood mononuclear cells from healthy volunteers (n = 13) who had previously received a smallpox vaccine (Dryvax) were activated and expanded using overlapping E3L peptides and their function, specificity and antiviral activity was analyzed. E3L-specific T cells were expanded from 7 of 12 (58.3%) vaccinated healthy donors. Twenty-five percent of these produced CD8+ T-cell responses and 87.5% produced CD4+ T cells. We identified epitopes restricted by HLA-B35 and HLA-DR15. Results: E3L-specific T cells killed peptide-loaded target cells as well as vaccinia-infected cells, but only CD8+ T cells could prevent the spread of infectious virus in virus inhibition assays. The epitopes recognized by E3L-specific T cells were shared with monkeypox, and although there was a single amino acid change in the variola epitope homolog, it was recognized by vaccinia-specific T-cells. Conclusions: It might be important to include E3L in any deletion mutant or subunit vaccine and E3L could provide a useful antigen to monitor protective immunity in humans.
Asunto(s)
Antígenos Virales/inmunología , Vacuna contra Viruela/inmunología , Viruela/inmunología , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/genética , Humanos , Interferón gamma/metabolismo , Leucocitos Mononucleares/inmunología , Péptidos/química , Péptidos/inmunología , Viruela/prevención & control , Donantes de Tejidos , Vacunación , Virus Vaccinia/genética , Virus Vaccinia/inmunología , Virión/inmunología , Replicación Viral/fisiologíaRESUMEN
As we reflect today on the eradication of smallpox 40 years ago, the greatest public health triumph in history, we’re reminded of what is possible when nations come together to confront a common foe, to confront a common enemy.
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Betacoronavirus , Infecciones por Coronavirus/prevención & control , Neumonía Viral/prevención & control , Pandemias/prevención & control , Cuarentena/organización & administración , Vacuna contra Viruela , Viruela/inmunologíaRESUMEN
The re-emergence of smallpox is an increasing and legitimate concern due to advances in synthetic biology. Vaccination programs against smallpox using the vaccinia virus vaccine ceased with the eradication of smallpox and, unlike many other countries, Australia did not use mass vaccinations. However, vaccinated migrants contribute to population immunity. Testing for vaccinia antibodies is not routinely performed in Australia, and few opportunities exist to estimate the level of residual population immunity against smallpox. Serological data on population immunity in Australia could inform management plans against a smallpox outbreak. Vaccinia antibodies were measured in 2003 in regular plasmapheresis donors at the Australian Red Cross Blood Service from New South Wales (NSW). The data were analysed to estimate the proportion of Australians in NSW with detectable serological immunity to vaccinia. The primary object of this study was to measure neutralising antibody titres against vaccinia virus. Titre levels in donor samples were determined by plaque reduction assay. To estimate current levels of immunity to smallpox infection, the decline in geometric mean titres (GMT) over time was projected using two values for the antibody levels estimated on the basis of different times since vaccination. The results of this study suggest that there is minimal residual immunity to the vaccinia virus in the Australian population. Although humoral immunity is protective against orthopoxvirus infections, cell-mediated immunity and immunological memory likely also play roles, which are not quantified by antibody levels. These data provide an immunological snapshot of the NSW population, which could inform emergency preparedness planning and outbreak control, especially concerning the stockpiling of vaccinia vaccine.
Asunto(s)
Vacuna contra Viruela/inmunología , Viruela/inmunología , Virus Vaccinia/inmunología , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Femenino , Humanos , Inmunidad Colectiva , Masculino , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , Estudios Seroepidemiológicos , Viruela/sangre , Viruela/epidemiología , Viruela/prevención & control , Vacuna contra Viruela/administración & dosificación , Factores de Tiempo , VacunaciónRESUMEN
The ancient technique of variolation (inoculation of the smallpox) which was introduced in the United States in 1721 was replaced by vaccination (inoculation of the cowpox) soon after the procedure was published by Edward Jenner in 1798. Benjamin Waterhouse is recognized as the introducer of smallpox vaccination in the United States having conducted the first vaccination in Boston on 8 July 1800, although other American physicians also played an important role in extending vaccination in the East Coast of the United States. A different route of introduction brought the smallpox vaccine from Mexico to New Mexico (March 1805) and Texas (April 1806) which at that time where part of the Viceroyalty of New Spain. The vaccine was brought to California in 1817 by Russian merchants who obtained it in Peru, where the vaccine had arrived in 1806 with the Spanish Philanthropic Expedition of the Vaccine. It took almost 150 years of vaccination efforts before the last natural outbreak of smallpox occurred in the United States in 1949.
Asunto(s)
Brotes de Enfermedades/historia , Inmunización/métodos , Poxviridae/inmunología , Vacuna contra Viruela/administración & dosificación , Viruela/prevención & control , Vacunación/métodos , Animales , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , Inmunización/historia , Poxviridae/aislamiento & purificación , Viruela/epidemiología , Viruela/inmunología , Vacuna contra Viruela/inmunología , Estados Unidos/epidemiología , Vacunación/historiaRESUMEN
Numerous animal models of systemic orthopoxvirus disease have been developed to evaluate therapeutics against variola virus (VARV), the causative agent of smallpox. These animal models do not resemble the disease presentation in human smallpox and most used surrogate Orthopoxviruses. A rodent model using VARV has a multitude of advantages, and previous investigations identified the CAST/EiJ mouse as highly susceptible to monkeypox virus infection, making it of interest to determine if these rodents are also susceptible to VARV infection. In this study, we inoculated CAST/EiJ mice with a range of VARV doses (102-106 plaque forming units). Some animals had detectable viable VARV from the oropharynx between days 3 and 12 post inoculation. Despite evidence of disease, the CAST/EiJ mouse does not provide a model for clinical smallpox due to mild signs of morbidity and limited skin lesions. However, in contrast to previous rodent models using VARV challenge (i.e. prairie dogs and SCID mice), a robust immune response was observed in the CAST/EiJ mice (measured by Immunoglobulin G enzyme-linked immunosorbent assay). This is an advantage of this model for the study of VARV and presents a unique potential for the study of the immunomodulatory pathways following VARV infection.
Asunto(s)
Modelos Animales de Enfermedad , Ratones , Viruela/inmunología , Virus de la Viruela/inmunología , Virus de la Viruela/patogenicidad , Animales , Femenino , Humanos , Ratones SCID , Viruela/fisiopatología , Viruela/virologíaRESUMEN
BACKGROUND: Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects. METHODS: To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio. RESULTS: A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm2 in the MVA group and 76.0 mm2 in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P<0.001). CONCLUSIONS: No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).
Asunto(s)
Anticuerpos Antivirales/sangre , Vacuna contra Viruela/inmunología , Viruela/prevención & control , Virus Vaccinia/inmunología , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Femenino , Humanos , Masculino , Viruela/inmunología , Vacuna contra Viruela/efectos adversos , Resultado del Tratamiento , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Adulto JovenRESUMEN
Concerns about bioterrorism and outbreaks of zoonotic orthopoxvirus require safe and efficacious smallpox vaccines. We previously reported the clinical efficacy and safety profiles of LC16m8, a live, attenuated, cell culture-derived, smallpox vaccine, examined in over 3000 healthy Japanese adults with various vaccination histories. In this study, serum of approximately 200 subjects pre and post LC16m8 vaccination were subjected to a vaccinia virus-specific protein array to evaluate the proteome-wide immunogenicity. The relationships between antigen-specific antibodies and plaque reduction neutralization titers were analyzed. LC16m8 induced antibodies to multiple vaccinia antigens in primary-vaccinated individuals and yielded effective booster responses in previously vaccinated individuals, demonstrating similar antibody profiles to those reported for other vaccinia virus strains. Several immunodominant antigens were indicated to be important for neutralization of the intracellular mature virion. The similarity of antibody profiles between LC16m8 and other smallpox vaccine strains supports the immunogenicity and protective efficacy of LC16m8.