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Purpose: The effectiveness of coronavirus disease 2019 (COVID-19) vaccination schemes and the combination of vaccines of various platforms for administering booster doses is still being studied since it will depend on the population's response to vaccines. We aimed to evaluate the safety, protection, and immunogenicity of the Salvadorean population's third dose booster COVID-19 vaccine and the potential benefit of homologous vs. heterologous regimens. Materials and Methods: This is an analytical observational cohort study in a population aged 18 to 65 years that was primarily vaccinated with AstraZeneca, Sinovac, or Pfizer/BioNTech. Volunteers were recruited (n=223) and followed up for 3 months after receiving the 3rd vaccine (BNT162b2) as a booster. Adverse reactions were monitored, serum anti-spike immunoglobulin G (IgG) was assessed by chemiluminescence, and a polymerase chain reaction was carried out when subjects developed clinical signs. Results: The cohorts finally included 199 participants, and we observed only mild adverse effects in all cohorts. A significant increase in specific IgG levels was found after the booster dose in all cohorts. The heterologous scheme with Sinovac showed the greatest increase in antibody titer, and a decrease was observed in all participants after 3 months. During the follow-up period, 30 participants showed symptomatology compatible with COVID-19, but only four were laboratory-confirmed and they showed mild clinical signs. Conclusion: These findings indicate that the booster doses used were safe and promoted an immediate increase in immunogenicity, which decreased over time. The heterologous regimen showed stronger immunogenicity compared to the messenger RNA-based homologous scheme.

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We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 µg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.

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We previously demonstrated the efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults in the SPECTRA phase 2/3 efficacy study. We extended the study to include 1278 healthy 12-17-year-old adolescents in Belgium, Colombia, and the Philippines who received either two doses of SCB-2019 or placebo 21 days apart, to assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 and variants of concern, and safety and reactogenicity as solicited and unsolicited adverse events with a comparator group of young adults (18-25 years). In participants with no evidence of prior SARS-CoV-2 infection SCB-2019 immunogenicity in adolescents was non-inferior to that in young adults; respective geometric mean neutralizing titers (GMT) against prototype SARS-CoV-2 14 days after the second vaccination were 271 IU/mL (95% CI: 211-348) and 144 IU/mL (116-178). Most adolescents (1077, 84.3%) had serologic evidence of prior SAR-CoV-2 exposure at baseline; in these seropositive adolescents neutralizing GMTs increased from 173 IU/mL (135-122) to 982 IU/mL (881-1094) after the second dose. Neutralizing titers against Delta and Omicron BA SARS-CoV-2 variants were also increased, most notably in those with prior exposure. SCB-2019 vaccine was well tolerated with generally mild or moderate, transient solicited and unsolicited adverse events that were comparable in adolescent vaccine and placebo groups except for injection site pain - reported after 20% of SCB-2019 and 7.3% of placebo injections. SCB-2019 vaccine was highly immunogenic against SARS-CoV-2 prototype and variants in adolescents, especially in those with evidence of prior exposure, with comparable immunogenicity to young adults. Clinical trial registration: EudraCT 2020-004272-17; ClinicalTrials.gov NCT04672395.

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Pertussis is a highly contagious respiratory disease caused by the Gram-negative bacterium Bordetella pertussis, which, although preventable by vaccination, still represents a public health problem today. Among the vaccines available, there are formulations with inactivated whole bacteria (wP) that generate lasting immunity, but may present adverse effects, and acellular formulations (aP), containing purified antigens and associated with milder adverse effects, but less lasting immunity. The adverse effects that may occur in wP were attributed to Lipooligosaccharide (LOS), present in outer membrane of B. pertussis. It is known that the structure of LOS can vary between strains and also that is a variation in the activation of TLR-4, which can lead to differences in the reactogenicity of vaccines. In 2015, the genomic sequencing of the vaccine strain of B. pertussis (Bp137) allowed the characterization of the Brazilian pertussis vaccine strain and the main genes related to the LOS synthesis pathway and some genes related to changes in Lipid A were described. “In silico” mapped genes whose products are linked to modifications in the acylated chains or in the phosphate group of Lipid A, such as pagL and pagP, and the lgm locus, related to the addition of glucosamine to the phosphate groups. These changes can lead to a greater or lesser activation of TLR-4 and production of cytokines, modulating the immune response. In this sense, the objective of this work was to deepen the characterization studies of the LOS of Bp137 to confirm whether the modifications found "in silico" actually occur in some in vivo condition, through the evaluation of the lgmA, pagP, pagL and waaC genes, related to the synthesis and modification of the LOS. The pertussis vaccine production strain Bp137 was cultivated on a laboratory scale, and accompanied by the in-process control steps commonly performed for the production of the pertussis vaccine. The pertussis vaccine production strain Bp137 was cultivated on a laboratory scale, and accompanied by the in-process control steps commonly performed for the production of the pertussis vaccine. From this culture, the extraction of total RNA was carried out, its concentration and purity were determined, for analysis of gene expression by conventional PCR and Real Time PCR. Bacterial growth was evidenced by Opacity and Optical Density; the specificity by purity tests, agglutinogens and Western blot of PT and FHA virulence factors. RNA with reasonable quality was obtained for gene expression analysis experiments and there was no genomic DNA. In the amplification of cDNA of Bp137, the amplification of the lgmA, pagP, pagL and waaC genes was observed, indicating that these genes are possibly expressed in Bp137. The Real Time PCR reactions confirmed the expression of lgmA in the Bp137 strain. As a future perspective, the expression by Real Time PCR for the target genes pagP, pagL and waaC should be confirmed. The results indicate that these genes are possibly ex- pressed in the Bp137 strain, but further studies are needed to obtain such confirmation. The characterization of B. pertussis LOS becomes even more important due to the possibility of using Lipid A as a vaccine adjuvant or even for future interventions to reduce vaccine reactogenicity.

A coqueluche é uma doença respiratória altamente contagiosa causada pela bactéria Gram-negativa Bordetella pertussis, que embora seja prevenível por vacinação, ainda hoje representa um problema de saúde pública. Dentre as vacinas disponíveis, há formulações com bactérias inteiras inativadas (wP) que geram imunidade duradoura, mas podem apresentar efeitos adversos, e formulações acelulares (aP), contendo an-tígenos purificados e associada a efeitos adversos mais leves, mas imunidade menos duradoura. Os efeitos adversos que podem ocorrer nas wP foram atribuídos ao Lipo-oligossacarídeo (LOS), presente na membrana externa de B. pertussis. Sabe-se que a estrutura do LOS pode variar entre cepas e também que há uma variação da ativa-ção de TLR-4, o que pode levar a diferenças na reatogenicidade das vacinas. Em 2015 o sequenciamento genômico da cepa vacinal de B. pertussis (Bp137) permitiu a caracterização da cepa produtora da vacina pertussis Brasileira e foram descritos os principais genes relacionados a via de síntese do LOS e alguns genes relacionados a modificações no Lipídio A. As análises “in silico” mapearam genes cujos produtos es-tão ligados a modificações nas cadeias aciladas ou ainda no grupo fosfato do Lipídio A, tais como pagL e pagP, e o locus lgm, relacionado a adição de glucosamina nos grupos fosfatos. Essas alterações podem levar a uma maior ou menor ativação de TLR-4 e produção de citocinas, modulando a resposta imune. Nesse sentido, objeti-vou-se com este trabalho aprofundar os estudos de caracterização do LOS da Bp137 para confirmar se as modificações encontradas “in silico” ocorrem de fato em alguma condição in vivo, através da avaliação dos genes lgmA, pagP, pagL e waaC, relacio-nados à síntese e modificação do LOS. A cepa de produção da vacina pertussis Bp137 foi cultivada em escala laboratorial, acompanhada das etapas de controle em processo comumente realizadas para a produção da vacina pertussis. A partir deste cultivo realizou-se a extração de RNA total, determinou-se sua concentração e pureza, para análise de expressão gênica por PCR convencional e PCR Em Tempo Real. O crescimento bacteriano foi evidenciado por meio da Opacidade e Densidade óptica; a especificidade pelos testes de pureza, aglutinógenos e Western Blot dos fatores de virulência PT e FHA. Obteve-se RNA com qualidade razoável para experimentos de análise de expressão gênica e verificou-se ausência de DNA genômico. Na amplificação de cDNA de Bp137, foi observada a amplificação dos genes lgmA, pagP, pagL e waaC, indicando que possivelmente estes genes estejam expressos na Bp137. As reações de PCR em Tempo Real confirmaram a expressão do lgmA na cepa Bp137. Como perspectiva futura deverá ser confirmada a expressão por PCR em Tempo Real para os genes alvo pagP, pagL e waaC. Os resultados indicam que possivelmente estes genes estejam expressos na cepa de Bp137, porém são necessários mais estudos para obter tal confirmação. A caracterização das LOS de B. pertussis se torna ainda mais importante ainda pela possibilidade do uso do Lipídio A como adjuvante vacinal ou ainda de futuras intervenções para redução da reatogenicidade vacinal.

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This is the first study outside of clinical trials (phase I-III) evaluating the ability of the Ad5-nCoV vaccine to generate neutralizing antibodies and the factors associated with optimal or suboptimal response. In a longitudinal assay, 346 people (117 with prior COVID-19 and 229 without prior COVID-19) vaccinated with Ad5-nCoV were recruited. The percentage of neutralizing antibodies against SARS-CoV-2 (Surrogate Virus Neutralization Test) and antibodies against Ad5 (ADV-Ad5 IgG ELISA) were quantified pre and post-vaccination effects. The Ad5-nCoV vaccine induces higher neutralizing antibodies percentage in individuals with prior COVID-19 than those without prior COVID-19 (median [IQR]: 98% [97-98.1] vs. 72% [54-90], respectively; p < 0.0001). Furthermore, a natural infection (before vaccination) induces more neutralizing antibodies percentage than immunized individuals without prior COVID-19 (p < 0.01). No patient had vaccine-severe adverse effects. The age, antidepressant, and immunosuppressive treatments, reactogenicity, and history of COVID-19 are associated with impaired antibody production. The anti-Ad5 antibodies increased after 21 days of post-vaccination in all groups (p < 0.01). We recommend the application of a booster dose of Ad5-nCoV, especially for those individuals without previous COVID-19 infection. Finally, the induction of anti-Ad5 antibodies after vaccination should be considered if a booster with the same vaccine is planned.

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Subjects receiving the same vaccine often show different levels of immune responses and some may even present adverse side effects to the vaccine. Systems vaccinology can combine omics data and machine learning techniques to obtain highly predictive signatures of vaccine immunogenicity and reactogenicity. Currently, several machine learning methods are already available to researchers with no background in bioinformatics. Here we described the four main steps to discover markers of vaccine immunogenicity and reactogenicity: (1) Preparing the data; (2) Selecting the vaccinees and relevant genes; (3) Choosing the algorithm; (4) Blind testing your model. With the increasing number of Systems Vaccinology datasets being generated, we expect that the accuracy and robustness of signatures of vaccine reactogenicity and immunogenicity will significantly improve.

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Combined vaccines for childhood are a strategy in the prevention of several diseases. These can maximize protection and decrease immunization schedules in children. New candidates are getting closer to being able to meet these needs, but they raise numerous strategic questions related to formulation and regulatory aspects. In addition to being immunogenic and protective must have low reactogenicity when combined with other antigens. Adjuvants are important components in achieving these combinations. Therefore, a reactogenicity study was designed for two Bordetella pertussis formulations containing hydroxide or aluminum phosphate in Sprague Dawley rats. Both formulations dose were administered in 0.2 mL intramuscularly. Clinical evaluations, body weight, water consumption, food, temperature, muscle volume, dermal irritability and pathological studies with special interest at the inoculation site were carried out. Only differences in body temperature and muscle volume were found with a slight increase in values with return to normal. The macroscopic study showed lesions at the site of inoculation, consid­ered characteristics of aluminum adjuvants, such as granulomatous abscesses and the increase in regional lymph nodes near the inoculation site. As conclusion, there are no differences between the formulations of B. pertussis with hydroxide or aluminum phosphate resulted in low reactogenicity.

Las vacunas combinadas resultan una estrategia importante en la obtención de vacunas múltiples para la infancia y el uso de adyuvantes es un componente de gran valor en lograr estas combinaciones, además de ser inmunogénicas y protectoras deben tener baja reactogenicidad, cuando se combinan con diferentes antígenos. Por esta razón, se diseñó un estudio de reactogenicidad a dos formulaciones que contenían hidróxido y fosfato de aluminio con antígenos de Bordetella pertussis en ratas Sprague Dawley. Se administró a cada grupo de ensayo una dosis correspondiente de ambas formulaciones en 0,2 mL por vía intramuscular. Se realizaron observaciones clínicas, comportamiento del peso corporal, consumo de agua, alimentos, temperatura corporal, volumen muscular, irritabilidad dérmica y estudios anatomopatológicos macroscópicos, con especial interés en el sitio de inoculación. No se observaron síntomas, ni muertes en los animales durante el estudio. Tampoco se encontraron diferencias entre los grupos experimentales en cuanto al peso corporal, el consumo de agua y de alimentos; los estudios de temperatura corporal y volumetría muscular evidenciaron un ligero incremento en los valores, los cuales involucionaron rápidamente a la normalidad. En el estudio anatomopatológico macroscópico se observaron lesiones a nivel del punto de inoculación, consideradas propias de los adyuvantes que contienen aluminio, tales como formaciones abscedadas de tipo granulomatosas y el aumento de los ganglios linfáticos regionales cercanos al punto de inoculación. Se concluye que las formulaciones en hidróxido y fosfato de aluminio con antígenos de B.pertussis resultaron ser de baja reactogenicidad.

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Introducción: la fiebre tifoidea es una infección sistémica causada por Salmonella tiphy, a través de la ingesta de alimentos contaminados (fecal-oral). Es un problema de salud pública, especialmente en países en vías de desarrollo. Objetivo: caracterizar la fiebre tifoidea en la provincia de Holguín durante los años 1972-2016. Método: se realizó un estudio descriptivo longitudinal de series de casos reportados de fiebre tifoidea por tarjeta EDO (Enfermedades de Declaración Obligatoria) en la provincia de Holguín desde el año 1972-2016. El universo estuvo constituido por 471 pacientes reportados por fiebre tifoidea, según tarjeta de EDO. Resultados: no se reportaron fallecidos desde el año 1974 y los menores de 15 años fueron los más afectados. El municipio que se mantuvo como de alto riesgo fue Holguín. La aplicación de la vacuna cubana de polisacárido Vi, mucho menos reactogénica y más efectiva que la utilizada anteriormente de calor-fenol, puede ser la causa o parte de la causa para la no ocurrencia de casos en los últimos 10 años en la provincia. Conclusiones: la morbilidad por fiebre tifoidea ha disminuido al igual que el número de brotes y afectados en brotes. Las medidas de control inmediatas y la existencia de un programa de control, además de la nueva vacuna de producción nacional, fabricada por los laboratorios Finlay, han hecho posible tales logros.

Introduction: typhoid fever is a systemic infection caused by Salmonella tiphy through ingestion of contaminated food (fecal-oral). It is a public health problem, especially in developing country. Objective: to characterize typhoid fever in Holguin province during the years 1972-2016. Method: a longitudinal descriptive study of series of reported cases of typhoid by EDO card (Notifiable Diseases) in Holguin province since 1972 to 2016, in order to characterize the typhoid in Holguin province was conducted. The universe consisted of 471 patients reported for typhoid Fever, according to EDO card. Results: no deaths were reported since 1974, children under 15 were the most affected, the Holguin municipality remained as high risk. The application of the Vi much less reactogenic and more effective polysaccharide Cuban vaccine used previously heat-phenol, may be the cause or part of the cause for the non-occurrence of cases in the last 10 years in the province. Conclusions: the morbidity due to typhoid fever has decreased as well as the number of outbreaks and affected in outbreaks. The immediate control measures and the existence of a control program, in addition to the new vaccine of national production, manufactured by the Finlay laboratories, have made such achievements possible.

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ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10) or subcutaneous (n=10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10) or B. abortus RB51 (n=10) and a negative (PBS+Montanide Gel01; n=10) control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

RESUMO: O presente estudo fornece as primeiras informações sobre a segurança de uma nova vacina usando o vetor viral influenza para expressar as proteínas de Brucella L7/L12 ou Omp16, contendo o adjuvante Montanide Gel01 em novilhas prenhes. A imunização de novilhas prenhes foi realizada através das vias conjuntiva (n=10) ou subcutânea (n=10), empregadas na primovacinação e na dose de reforço. O intervalo foi de 28 dias. A vacina empregando o vetor foi comparada com os grupos de controle positivo, vacinados com B. abortus B19 (n=10) ou B. abortus RB51 (n=10) e um grupo de controle negativo (PBS + Montanide Gel01; n=10). Os estudos clínicos, termometria, reação local e observação do aborto mostraram que a vacina empregando o vetor, aplicada pela via conjuntival ou subcutânea, foi completamente segura para novilhas prenhes, em comparação com as vacinas comerciais B. abortus B19 ou B. abortus RB51. O único efeito adverso foi a formação de infiltrado no local da administração subcutânea; essa reação não foi observada no grupo vacinado pela via conjuntival.

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ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10) or subcutaneous (n=10) route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10) or B. abortus RB51 (n=10) and a negative (PBS+Montanide Gel01; n=10) control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

RESUMO: O presente estudo fornece as primeiras informações sobre a segurança de uma nova vacina usando o vetor viral influenza para expressar as proteínas de Brucella L7/L12 ou Omp16, contendo o adjuvante Montanide Gel01 em novilhas prenhes. A imunização de novilhas prenhes foi realizada através das vias conjuntiva (n=10) ou subcutânea (n=10), empregadas na primovacinação e na dose de reforço. O intervalo foi de 28 dias. A vacina empregando o vetor foi comparada com os grupos de controle positivo, vacinados com B. abortus B19 (n=10) ou B. abortus RB51 (n=10) e um grupo de controle negativo (PBS + Montanide Gel01; n=10). Os estudos clínicos, termometria, reação local e observação do aborto mostraram que a vacina empregando o vetor, aplicada pela via conjuntival ou subcutânea, foi completamente segura para novilhas prenhes, em comparação com as vacinas comerciais B. abortus B19 ou B. abortus RB51. O único efeito adverso foi a formação de infiltrado no local da administração subcutânea; essa reação não foi observada no grupo vacinado pela via conjuntival.