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Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.
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RESUMEN INTRODUCCIÓN: El dengue constituye un problema emergente en Argentina. En la provincia de Buenos Aires se inició un primer brote en 2016, y el de 2020 registró un 82% más de casos y afectó municipios sin antecedentes previos. El objetivo de este estudio fue caracterizar la dinámica de los brotes bonaerenses de 2016 y 2020 . MÉTODOS: Se realizó un estudio descriptivo, retrospectivo y transversal. Los casos fueron registrados en el Sistema Nacional de Vigilancia de la Salud. Fueron calculadas las distribuciones de frecuencia de los casos notificados, considerando también el origen: importados o autóctonos. Las tasas de incidencia y las razones de tasas se calcularon por Región Sanitaria. La difusión de la onda epidémica para ambos brotes fue obtenida mediante el cálculo de métricas adimensionales . RESULTADOS: Ambos brotes manifestaron ondas de similar comportamiento, pero con diferente expansión temporal y velocidades de difusión que se distanciaron en el inicio y luego hacia el final, presentando el último brote una mayor incidencia pero con una tasa de propagación de menor variación . DISCUSIÓN: La investigación realizada permitió caracterizar los brotes ocurridos en 2016 y 2020, y focalizar regionalmente la incidencia del fenómeno reemergente de la infección por arbovirus dengue (principalmente DEN-1 circulante) en la provincia de Buenos Aires, con cifras de incidencia que superaron lo conocido en la historia de la enfermedad en Argentina.
ABSTRACT INTRODUCTION: Dengue is an emerging problem in Argentina. In the province of Buenos Aires, the first outbreak was in 2016, and the one occurred during 2020 caused 82% more cases and affected districts with no previous cases. The objective of this study was to characterize the outbreak dynamics in the province of Buenos Aires in 2016 and 2020 . METHODS: A descriptive, retrospective and crosssectional study was conducted. The cases were registered in the National Health Surveillance System. The frequency distributions of the reported cases were calculated, considering also the origin: imported or autochthonous. Incidence rates and rate ratios were calculated for each Health Region. The diffusion of the epidemic wave for both outbreaks was obtained by calculating dimensionless metrics . RESULTS: Both outbreaks showed waves with similar behavior, but with different temporal expansion and diffusion speeds that distanced from each other at the beginning and then towards the end. The last outbreak had a higher incidence, but a propagation rate with less variation . DISCUSSION: This research allowed to characterize the two outbreaks occurred in 2016 and 2020, and to focus regionally on the incidence of the re-emerging phenomenon of dengue arbovirus infection (mainly circulating DEN-1) in the province of Buenos Aires, with incidence figures that exceeded those known in the history of the disease in Argentina.
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RESUMEN INTRODUCCIÓN El impacto de la pandemia por COVID-19 sobre la mortalidad abarca tanto sus efectos directos, las defunciones atribuidas al virus SARS-CoV-2, como indirectos sobre otras causas de muerte. "El objetivo del estudio fue determinar la variación sobre causas de muerte no COVID-19 en la provincia de Buenos Aires durante 2020 MÉTODOS Se realizó un estudio descriptivo de base poblacional, utilizando fuentes secundarias. Se analizó la variación en la mortalidad por causas específicas codificadas según CIE-10, desagregadas a nivel de capítulo y grupos. Las variaciones entre las causas de muerte observadas y esperadas se compararon mediante el método de P-score respecto al quinquenio inmediato anterior (2015-2019) RESULTADOS Todos los capítulos CIE-10 estudiados se ubican por debajo del promedio de la serie histórica. La mayor variación se registra en causas externas (-20,0%), enfermedades del sistema respiratorio (-9,1%), tumores (-8,1%), enfermedades nutricionales, endocrinas y metabólicas (-5,7%) y finalmente enfermedades del sistema circulatorio (-2,2%) DISCUSIÓN Se observó la existencia de un reemplazo variable de otras causas de defunción por muertes COVID-19 durante 2020. El análisis de causas múltiples resultó de utilidad para reestimar, en el caso del grupo de influenza (gripe) y neumonías, la participación global de la COVID-19 en la cadena de eventos que contribuyeron al deceso.
ABSTRACT INTRODUCTION The impact of the COVID-19 pandemic on mortality encompasses both its direct effects, deaths attributed to the SARS-CoV-2 virus, as well as indirect on other causes of death. The objective of the study was to determine the variation in non- COVID-19 causes of death in the province of Buenos Aires during 2020 METHODS A population-based descriptive study was carried out using secondary sources. Specific causes of death coded according to ICD-10, disaggregated by chapter and group, were analyzed. To determine whether there were variations between the observed and expected causes of death, the values of the study period were compared with the immediately preceding five-year period (2015-2019) using the P-score method RESULTS All the ICD-10 chapters studied are below the average of the historical series. The greatest variation appears in the chapter External Causes (-20.0%), Diseases of the Respiratory System (-9.1%), Neoplasms (-8.1%), Endocrine, Nutritional and Metabolic Diseases (-5.7%) and, finally, Diseases of the Circulatory System (-2.2%) DISCUSSION There is a variable change of other causes of death by COVID-19 deaths during 2020. The analysis of multiple causes was useful to re-estimate, in the case of the group of influenza (flu) and pneumonia, the global participation of COVID-19 in the chain of events that contributed to the death.
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RESUMEN INTRODUCCIÓN Uno de los problemas que ha enfrentado el sistema de salud de los diferentes países debido a la pandemia de COVID-19 es la disponibilidad de servicios y atención médica en unidades de cuidados intensivos (UCI). El objetivo fue evaluar la sobrevida en pacientes internados por COVID-19 en UCI entre enero y abril de 2021 en la provincia de Buenos Aires, Argentina MÉTODOS Se consideró a los pacientes que, incluidos en el sistema de vigilancia, tuvieran su correlato de información del porcentaje ocupacional de camas de la UCI desde el sistema general. Con esta información se realizó un análisis de sobrevida, considerando tablas de vida, Kaplan-Meier y regresión de Cox. El evento fue el óbito, el tiempo de seguimiento a 96 días y las fechas de internación, defunción y egreso dentro de la UCI como períodos individuales de cada paciente. La capacidad operativa de las UCI fue medida a través del porcentaje de ocupación de camas al momento del ingreso RESULTADOS Las UCI con un porcentaje ocupacional mayor al 80% mostraron pacientes con menor curva de sobrevida que sus pares por debajo de esas cifras al momento de ingresar a la internación DISCUSIÓN Las diferencias en promedios de sobrevida son estadísticamente diferentes, y muestran dos curvas distintas de supervivencia en el momento en que la segunda ola de COVID-19 afectaba a la Argentina. ^s+
ABSTRACT INTRODUCTION One of the problems faced by the health system in different countries due to COVID-19 pandemic is the availability of medical care services in intensive care units (ICU). The objective was to evaluate survival in patients hospitalized for COVID-19 in the ICUs during the period January-April 2021 in the province of Buenos Aires METHODS Patients included in the surveillance system who had their correlate of information on percentage of bed occupancy in the ICUs from the general system were considered. With this information, a survival analysis was performed, considering life tables, Kaplan-Meier and Cox regression. The event was death, the 96-day follow-up and the dates of admission, death and discharge within the ICUs as individual periods for each patient. Inpatient capacity of the ICUs was measured through the percentage of bed occupancy at the time of admission RESULTS The ICUs with a bed occupancy greater than 80% showed patients with a lower survival curve than those below that figure at the time of admission DISCUSSION The differences in average survival were statistically significant, and show two different survival curves at the time the second wave of COVID-19 affected the country.
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RESUMEN INTRODUCCIÓN El desarrollo de la pandemia por COVID-19 se ha descrito en función de olas. El objetivo del trabajo fue caracterizar la pandemia en la provincia de Buenos Aires a través de la comparación de indicadores en cada ola MÉTODOS Se realizó un estudio descriptivo observacional con datos de fuentes secundarias. Cada ola se definió a partir de los puntos de inflexión en la curva de casos confirmados acumulados. Las olas se compararon por indicadores de morbilidad y mortalidad RESULTADOS Se establecieron tres períodos distintos: primera ola, rebrote de verano y segunda ola. El máximo de casos confirmados y fallecidos diarios en la primera ola fue 5799 y 192, y en la segunda, 12 141 y 282, respectivamente. La letalidad fue 3,5% en la primera ola y 2,3% en la segunda. La edad media en los casos confirmados y fallecidos en la segunda ola fue significativamente menor que en la primera. En los casos confirmados, la mayor diferencia en la proporción por grupos etarios se observó en el de 10-19 años DISCUSIÓN La segunda ola tuvo mayor magnitud, posiblemente relacionada con la circulación de una nueva variante del SARS-CoV-2, Gamma (P.1), para la cual hay evidencias de mayor transmisibilidad. El descenso de edad en fallecidos podría explicarse por la disminución en la edad de los casos confirmados y por la priorización de personas de mayor edad en el plan de vacunación. El aumento en el grupo de 10-19 años podría relacionarse con el reinicio de clases presenciales en las escuelas. ^s+
ABSTRACT INTRODUCTION The development of the COVID-19 pandemic has been described in terms of waves. This work aimed at characterizing the pandemic in the province of Buenos Aires through the comparison of indicators in each wave METHODS A descriptive observational study with data from secondary sources was conducted. Each wave was defined based on the inflection points of the cumulative confirmed cases curve. The waves were compared by indicators of morbidity and mortality RESULTS Three different periods were established: first wave, summer resurgence and second wave. The maximum number of confirmed cases and deaths per day during the first wave was 5799 and 192, and during the second wave 12141 and 282, respectively. The fatality was 3.5% during the first wave and 2.3% during the second one. The mean age of confirmed and deceased cases during the second wave was significantly lower than during the first one. Among confirmed cases, the greatest difference in the proportion by age group was observed in the group aged 10 to 19 years DISCUSSION The second wave was of greater magnitude, probably due to the circulation of the new variant of SARS-CoV-2, Gamma (P.1), for which there is evidence of increased transmissibility. The decrease in the age of deceased may be explained by the decrease in the age of confirmed cases and by the priority given to older people in the vaccination campaign. The increase in the 10-19 age group may be related to the resumption of face-to-face classes in schools.
ABSTRACT
INTRODUCCIÓN: El desarrollo de la pandemia por COVID-19 se ha descrito en función de olas. El objetivo del trabajo fue caracterizar la pandemia en la provincia de Buenos Aires a través de la comparación de indicadores en cada ola. MÉTODOS: Se realizó un estudio descriptivo observacional con datos de fuentes secundarias. Cada ola se definió a partir de los puntos de inflexión en la curva de casos confirmados acumulados. Las olas se compararon por indicadores de morbilidad y mortalidad. RESULTADOS: Se establecieron tres períodos distintos: primera ola, rebrote de verano y segunda ola. El máximo de casos confirmados y fallecidos diarios en la primera ola fue 5799 y 192, y en la segunda, 12 141 y 282, respectivamente. La letalidad fue 3,5% en la primera ola y 2,3% en la segunda. La edad media en los casos confirmados y fallecidos en la segunda ola fue significativamente menor que en la primera. En los casos confirmados, la mayor diferencia en la proporción por grupos etarios se observó en el de 10-19 años. DISCUSIÓN: La segunda ola tuvo mayor magnitud, posiblemente relacionada con la circulación de una nueva variante del SARS-CoV-2, Gamma (P.1), para la cual hay evidencias de mayor transmisibilidad. El descenso de edad en fallecidos podría explicarse por la disminución en la edad de los casos confirmados y por la priorización de personas de mayor edad en el plan de vacunación. El aumento en el grupo de 10-19 años podría relacionarse con el reinicio de clases presenciales en las escuelas.
Subject(s)
Argentina , Epidemiology , COVID-19ABSTRACT
INTRODUCCIÓN: Uno de los problemas que ha enfrentado el sistema de salud de los diferentes países debido a la pandemia de COVID-19 es la disponibilidad de servicios y atención médica en unidades de cuidados intensivos (UCI). El objetivo fue evaluar la sobrevida en pacientes internados por COVID-19 en UCI entre enero y abril de 2021 en la provincia de Buenos Aires, Argentina. MÉTODOS: Se consideró a los pacientes que, incluidos en el sistema de vigilancia, tuvieran su correlato de información del porcentaje ocupacional de camas de la UCI desde el sistema general. Con esta información se realizó un análisis de sobrevida, considerando tablas de vida, Kaplan-Meier y regresión de Cox. El evento fue el óbito, el tiempo de seguimiento a 96 días y las fechas de internación, defunción y egreso dentro de la UCI como períodos individuales de cada paciente. La capacidad operativa de las UCI fue medida a través del porcentaje de ocupación de camas al momento del ingreso. RESULTADOS: Las UCI con un porcentaje ocupacional mayor al 80% mostraron pacientes con menor curva de sobrevida que sus pares por debajo de esas cifras al momento de ingresar a la internación. DISCUSIÓN: Las diferencias en promedios de sobrevida son estadísticamente diferentes, y muestran dos curvas distintas de supervivencia en el momento en que la segunda ola de COVID-19 afectaba a la Argentina.
Subject(s)
Argentina , Survival , COVID-19 , Intensive Care UnitsABSTRACT
La pandemia por COVID-19 iniciada en 2020 continúa ejerciendo presión sobre los sistemas de salud de los países y, en conjunto con las políticas impulsadas por los gobiernos para morigerar su impacto, ha alterado los hábitos en la población. De este modo, además de los efectos conocidos de la enfermedad sobre los contagios y defunciones directamente atribuidos a la misma, se espera que la pandemia haya intervenido sobre el proceso de salud-enfermedad-atención impactando indirectamente en otras causas de muerte. Atendiendo a este fenómeno, el objetivo de la presente investigación es indagar cómo la pandemia por COVID-19 afectó la mortalidad por causas específicas tratables, y su relación con las intervenciones y consultas en efectores de salud, durante el período 2020-2021 en la provincia de Buenos Aires. Para ello, se efectuó un estudio descriptivo retrospectivo de base poblacional a partir de fuentes de datos secundarias; incluyendo en el universo del estudio a la totalidad de eventos de atención registrados en el sistema de salud público y la totalidad de defunciones con ocurrencia en la Provincia desde el 01/01/2020 al 31/12/2021.
Subject(s)
Public Health Systems , COVID-19ABSTRACT
Pertussis resurgence had been attributed to waning vaccine immunity and Bordetella pertussis adaptation to escape vaccine-induced immunity. Circulating bacteria differ genotypically from strains used in production of pertussis vaccine. Pertactin-deficient strains are highly prevalent in countries that use acellular vaccine (aP), suggesting strong aP-imposed selection of circulating bacteria. To corroborate this hypothesis, systematic studies on pertactin prevalence of infection in countries using whole-cell vaccine are needed. We provide pertussis epidemiologic data and molecular characterization of B. pertussis isolates from Buenos Aires, Argentina, during 2000-2017. This area used primary vaccination with whole-cell vaccine. Since 2002, pertussis case incidences increased at regular 4-year outbreaks; most cases were in infants <1 year of age. Of the B. pertussis isolates analyzed, 90.6% (317/350) contained the ptxP3-ptxA1-prn2-fim3-2 allelic profile. Immunoblotting and sequencing techniques detected only the 2 pertactin-deficient isolates. The low prevalence of pertactin-deficient strains in Argentina suggests that loss of pertactin gene expression might be driven by aP vaccine.
Subject(s)
Bacterial Outer Membrane Proteins/genetics , Bordetella pertussis/classification , Bordetella pertussis/genetics , Gene Deletion , Virulence Factors, Bordetella/genetics , Whooping Cough/epidemiology , Whooping Cough/microbiology , Argentina/epidemiology , Bacterial Outer Membrane Proteins/immunology , Bordetella pertussis/immunology , Child , Child, Preschool , Genotype , Humans , Infant , Pertussis Vaccine/administration & dosage , Pertussis Vaccine/immunology , Public Health Surveillance , Serogroup , Virulence Factors, Bordetella/immunology , Whooping Cough/diagnosis , Whooping Cough/prevention & controlABSTRACT
Pertussis is a respiratory infectious disease that has been resurged during the last decades. The change from the traditional multi-antigen whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines that consist of a few antigens formulated with alum, appears to be a key factor in the resurgence of pertussis in many countries. Though current aP vaccines have helped to reduce the morbidity and mortality associated with pertussis, they do not provide durable immunity or adequate protection against the disease caused by the current circulating strains of Bordetella pertussis, which have evolved in the face of the selection pressure induced by the vaccines. Based on the hypothesis that a new vaccine containing multiple antigens could overcome deficiencies in the current aP vaccines, we have designed and characterized a vaccine candidate based on outer membrane vesicle (OMVs). Here we show that the OMVs vaccine, but not an aP vaccine, protected mice against lung infection with a circulating pertactin (PRN)-deficient isolate. Using isogenic bacteria that in principle only differ in PRN expression, we found that deficiency in PRN appears to be largely responsible for the failure of the aP vaccine to protect against this circulating clinical isolates. Regarding the durability of induced immunity, we have already reported that the OMV vaccine is able to induce long-lasting immune responses that effectively prevent infection with B. pertussis. Consistent with this, here we found that CD4 T cells with a tissue-resident memory (TRM) cell phenotype (CD44+CD62LlowCD69+ and/or CD103+) accumulated in the lungs of mice 14 days after immunization with 2 doses of the OMVs vaccine. CD4 TRM cells, which have previously been shown to play a critical role sustained protective immunity against B. pertussis, were also detected in mice immunized with wP vaccine, but not in the animals immunized with a commercial aP vaccine. The CD4 TRM cells secreted IFN-γ and IL-17 and were significantly expanded through local proliferation following respiratory challenge of mice with B. pertussis. Our findings that the OMVs vaccine induce respiratory CD4 TRM cells may explain the ability of this vaccine to induce long-term protection and is therefore an ideal candidate for a third generation vaccine against B. pertussis.
Subject(s)
Bordetella pertussis/immunology , CD4-Positive T-Lymphocytes/immunology , Exosomes/immunology , Immunologic Memory , Pertussis Vaccine/immunology , Whooping Cough/prevention & control , Animals , Cytokines/metabolism , Disease Models, Animal , Immunologic Factors/metabolism , Mice , Pertussis Vaccine/administration & dosage , Vaccines, Acellular/administration & dosage , Vaccines, Acellular/immunologyABSTRACT
Bordetella parapertussis is a respiratory-disease pathogen producing symptomatology similar to that of pertussis but of underestimated incidence and with no specific vaccine existing. We recently designed a vaccine candidate from B. parapertussis outer-membrane vesicles (OMVs) that proved to be safe and protective in a murine-infection model. Based on protection recently reported for the B. parapertussis O antigen in aqueous solution, we assessed here whether the B. parapertussis O-antigen-containing lipopolysaccharide (BppLPS-O+) embedded in the membranes, as present in B. parapertussis-derived OMVs (OMVs(Bpp-LPS-O+)), was the component responsible for that previously observed protection by OMVs. By performing a comparative study with OMVs from a human strain with undetectable O antigen (OMVs(Bpp-LPS-O-)), we demonstrated that the OMVs(Bpp-LPS-O+), but not the OMVs(Bpp-LPS-O-), protected mice against sublethal B. parapertussis infections. Indeed, the B. parapertussis loads were significantly reduced in the lungs of OMVs(Bpp-LPS-O+) -vaccinated animals, with the CFUs recovered being decreased by 4 log units below those detected in the non-immunized animals or in the animals treated with the OMVs(Bpp-LPS-O-), (p < 0.001). We detected that the OMVs(Bpp-LPS-O+) induced IgG antibodies against B. parapertussis whole-cell lysates, which immunocomponents recognized, among others, the O antigen and accordingly conferred protection against B. parapertussis infection, as observed in in-vivo-passive-transfer experiments. Of interest was that the OMVs(Bpp-LPS-O+) -generated sera had opsonophagocytic and bactericidal capabilities that were not detected with the OMVs(Bpp-LPS-O-)-induced sera, suggesting that those activities were involved in the clearance of B. parapertussis. Though stimulation of cultured spleen cells from immunized mice with formulations containing the O antigen resulted in gamma interferon (IFN-γ) and interleukin-17 production, spleen cells from OMVs(Bpp-LPS-O+) -immunized mice did not significantly contribute to the observed protection against B. parapertussis infection. The protective capability of the B. parapertussis O antigen was also detected in formulations containing both the OMVs derived from B. pertussis and purified BppLPS-O+. This combined formulation protected mice against B. pertussis along with B. parapertussis.
Subject(s)
Bacterial Vaccines/immunology , Bordetella Infections/immunology , Bordetella parapertussis/physiology , Bordetella pertussis/physiology , O Antigens/immunology , Animals , Antibodies, Bacterial/blood , Bacterial Outer Membrane Proteins/metabolism , Cell-Derived Microparticles/metabolism , Disease Resistance , Female , Humans , Immunity, Heterologous , Immunization, Passive , Interferon-gamma/metabolism , Interleukin-17/metabolism , Lymphocyte Activation , Mice , Mice, Inbred BALB C , O Antigens/metabolism , VaccinationABSTRACT
Maternal safety through pertussis vaccination and subsequent maternal-fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP) vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4-5 logs, p < 0.001) in the colony-forming-units recovered from the lungs of 16-week-old offspring. Moreover, maternal-vaccination-acquired immunity from the first pregnancy still conferred protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results-though admittedly not necessarily immediately extrapolatable to humans-nevertheless enabled us to test hypotheses under controlled conditions through detailed sampling and data collection. These findings will hopefully refine hypotheses that can then be validated in subsequent human studies.
ABSTRACT
Pertussis has resurged during the last two decades in different countries. In particular in the 2010-2013 period large outbreaks were detected in US, Australia, UK and The Netherlands with significant mortality in infants. The epidemiological situation of pertussis points out the need to develop new vaccines and in this regard we previously developed a new vaccine based on outer membrane vesicles (OMVs) which have been shown to be safe and to induce protection in mice. Here we have further investigated the properties of OMVs vaccines; in particular we studied the contribution of pertussis toxin (PTx) and pertactin (Prn) in OMVs-mediated protection against pertussis. PTx-deficient OMVs and Prn-deficient OMVs were obtained from defective Bordetella pertussis mutants. The absence of PTx or Prn did compromise the protective capacity of the OMVs formulated as Tdap vaccine. Whereas the protective efficacy of the PTx-deficient OMVs in mice was comparable to Prn-deficient OMVs, the protective capacity of both of them was significantly impaired when it was compared with the wild type OMVs. Interestingly, using OMVs obtained from a B. pertussis strain which does not express any of the virulence factors but expresses the avirulent phenotype; we observed that the protective ability of such OMVs was lower than that of OMVs obtained from virulent B. pertussis phase. However, it was surprising that although the protective capacity of avirulent OMVs was lower, they were still protective in the used mice model. These results allow us to hypothesize that OMVs from avirulent phase shares protective components with all OMVs assayed. Using an immune proteomic strategy we identified some common components that could play an important role in protection against pertussis.
Subject(s)
Bacterial Outer Membrane Proteins/immunology , Pertussis Toxin/immunology , Pertussis Vaccine/immunology , Virulence Factors, Bordetella/immunology , Whooping Cough/prevention & control , Animals , Antigens, Bacterial/immunology , Female , Mice, Inbred BALB CABSTRACT
Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs(BpPagL)) are good vaccine candidates to protect against pertussis. In this work the OMVs(BpPagL) formulated with diphtheria and tetanus toxoids (Tdap(OMVsBpPagL)) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap(OMVsBpPagL) and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap(OMVsBpPagL) were performed. With the normalized doses of both vaccines we observed that Tdap(OMVsBpPagL) protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap(OMVsBpPagL) protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap(OMVsBpPagL) induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap(OMVsBpPagL) is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.
