Session V: Getting Vaccines to the Market: Case studies

This is a presentation of Session V. (No Abstract

A Herpes Simplex Virus 2 (HSV-2) Glycoprotein D-expressing Nonreplicating Dominant-Negative HSV-2 Virus Vaccine Is Superior to a gD2 Subunit Vaccine against HSV-2 Genital Infection in Guinea Pigs

We recently constructed a novel non-replicating dominant-negative HSV-2 recombinant viral vaccine (CJ2-gD2) capable of expressing various HSV-2 antigens that are dominant targets of HSV-2-specific CD8 T-cell response. Importantly, CJ2-gD2 expresses gD2, the HSV-2 major antigen glycoprotein D, as efficiently as wild-type HSV-2 infection and can lead to a nearly 500-fold reduction in wild-type HSV-2 viral replication in cells co-infected with CJ2-gD2 and wild-type HSV-2. In this report, we show that CJ2-gD2 elicits a strong antibody response to various HSV-2 antigens and is highly effective in the prevention of primary and recurrent HSV-2 genital infection and disease in the immunized guinea pigs. The direct comparison study between CJ2-gD2 and a gD2 subunit vaccine (gD2-alum/MPL) with a formulation akin to a vaccine tested in phase III clinical trials shows that CJ2-gD2 is 8 times more effective than the gD2-alum/MPL subunit vaccine in eliciting an anti-HSV-2 specific neutralizing antibody response and offers significantly superior protection against primary and recurrent HSV-2 genital infections. Importantly, no challenge wild-type HSV-2 viral DNA was detectable in dorsal root ganglia DNA isolated from CJ2-gD2-immunized guinea pigs on day 60 post-challenge. CJ2-gD2 should be an excellent HSV-2 vaccine candidate for protection against HSV-2 genital infection and disease in humans

Evaluación de la respuesta estructural en una edificación aporticada, con sistema constructivo de losas U-Boot Beton, losa Vigacero y una convencional, Trujillo – 2022

La presente investigación es la evaluación de la respuesta estructural en una edificación aporticada con un sistema constructivo de losas U-Boot Beton, losa Vigacero y convencional en la ciudad de Trujillo. La metodología a emplear es de tipo no experimental aplicada porque ya existen enfoques teóricos a cerca de las variables a través de un diseño transversal. Los resultados obtenidos en la presente investigación es que la Losa U Boot Beton – Losa Vigacero respecto a costo, tiempo y seguridad en edificación es mejor que la losa aporticado convencional. Para este estudio se empleó un diseño no experimental, del tipo transversal descriptivo, en donde la población y la muestra se determinó mediante la técnica de Muestreo No Probabilístico Intencional, la técnica de observación, con la ayuda de un programa computacional para la medición de los objetivos. Finalmente se presentó la evaluación del desempeño sísmico según los objetivos básicos de desempeño recomendados por el Comité Visión 2000. Así, se constató que el 100% de las edificaciones no cumplen con el objetivo de totalmente operacional para el sismo frecuente, el 37% cumplen con el objetivo de operacional para el sismo de servicio, el 6% cumplen con el objetivo de seguridad de vida para el sismo de diseño, y el 100% de las edificaciones no cumplen con el objetivo de prevención de colapso para el sismo máximo.The present investigation is the evaluation of the structural response in a framed building with a construction system of U-Boot Beton slabs, Vigacero and conventional slabs in the city of Trujillo. The methodology to be used is of a non-experimental type applied because there are already theoretical approaches to the variables through a cross-sectional design. The results obtained in the present investigation is that the U Boot Beton Slab - Vigacero Slab with respect to cost, time and safety in construction is better than the conventional framed slab. For this study, a non-experimental design was used, of the descriptive cross-sectional type, where the population and the sample were determined by means of the Intentional Non-Probabilistic Sampling technique, the observation technique, with the help of a computer program for the measurement of the objectives. Finally, the seismic performance evaluation was presented according to the basic performance objectives recommended by the Vision 2000 Committee. Thus, it was found that 100% of the buildings do not meet the goal of being fully operational for frequent earthquakes, 37% meet the the operational objective for the service earthquake, 6% meet the life safety objective for the design earthquake, and 100% of the buildings do not meet the collapse prevention objective for the maximum earthquake

Effector and Central Memory Poly-Functional CD4+ and CD8+ T Cells are Boosted upon ZOSTAVAX® Vaccination

ZOSTAVAX® is a live attenuated varicella-zoster virus (VZV) vaccine that is licensed for the protection of individuals ≥ 50 years against shingles, and its most common complication, post-herpetic neuralgia. While IFN responses increase upon vaccination, the quality of the T cell response has not been elucidated. By using polychromatic flow cytometry, we characterized the breadth, magnitude, and quality of ex vivo CD4+ and CD8+ T cell responses induced 3 – 4 weeks after ZOSTAVAX vaccination of healthy adults. We show, for the first time that the highest frequencies of VZV-specific CD4+ T cells were poly-functional CD154+IFNγ+IL-2+TNFα+ cells, which were boosted upon vaccination. The CD4+ T cells were broadly reactive to several VZV proteins, with IE63 ranking the highest amongst them in the fold-rise of poly-functional cells, followed by IE62, gB, ORF9, and gE. We identified a novel poly-functional ORF9-specific CD8+ T cell population in 62% of the subjects, and these were boosted upon vaccination. Poly-functional CD4+ and CD8+ T cells produced significantly higher levels of IFNγ, IL-2, and TNFα compared to mono-functional cells. After vaccination, a boost in the expression of IFN by poly-functional IE63-and ORF9-specific CD4+ T cells, and IFNγ, IL-2, and TNFα by ORF9-specific poly-functional CD8+ T cells was observed. Responding poly-functional T cells exhibited both effector (CCR7−CD45RA−CD45RO+), and central (CCR7+CD45RA−CD45RO+) memory phenotypes, which expressed comparable levels of cytokines. Altogether, our studies demonstrate that a boost in memory poly-functional CD4+ T cells, and ORF9-specific CD8+ T cells may contribute towards ZOSTAVAX efficacy

Optical Measurement and Aerosol Filter Loading for Climate Studies.

Workshop CV Dust Atmospheric Aerosols in Cape Verde Region. Aveiro, 11 Janeiro 2013

Vaccination with Ad5 Vectors Expands Ad5-Specific CD8+ T Cells without Altering Memory Phenotype or Functionality

Adenoviral (Ad) vaccine vectors represent both a vehicle to present a novel antigen to the immune system as well as restimulation of immune responses against the Ad vector itself. To what degree Ad-specific CD8(+) T cells are restimulated by Ad vector vaccination is unclear, although such knowledge would be important as vector-specific CD8(+) T cell expansion could potentially further limit Ad vaccine efficacy beyond Ad-specific neutralizing antibody alone.Here we addressed this issue by measuring human Adenovirus serotype 5 (Ad5)-specific CD8(+) T cells in recipients of the Merck Ad5 HIV-1 vaccine vector before, during, and after vaccination by multicolor flow cytometry. Ad5-specific CD8(+) T-cells were detectable in 95% of subjects prior to vaccination, and displayed primarily an effector-type functional profile and phenotype. Peripheral blood Ad5-specific CD8(+) T-cell numbers expanded after Ad5-HIV vaccination in all subjects, but differential expansion kinetics were noted in some baseline Ad5-neutralizing antibody (Ad5 nAb) seronegative subjects compared to baseline Ad5 nAb seropositive subjects. However, in neither group did vaccination alter polyfunctionality, mucosal targeting marker expression, or memory phenotype of Ad5-specific CD8(+) T-cells.These data indicate that repeat Ad5-vector administration in humans expands Ad5-specific CD8(+) T-cells without overtly affecting their functional capacity or phenotypic properties. This is a secondary analysis of samples collected during the 016 trial. Results of the Merck 016 trial safety and immunogenicity have been previously published in the journal of clinical infectious diseases [1].ClinicalTrials.gov NCT00849680[http://www.clinicaltrials.gov/show/NCT00849680]

Visita domiciliar em um condomínio de idosos como instrumento para atenção e cuidado integral à saúde / Home visit in an elderly condominium as an instrument for integral health care and care

O envelhecimento humano é um fenômeno natural, social e irreversível. É dever do Estado a garantia do envelhecimento saudável e com condições dignas. O presente estudo tem como objetivo descrever as experiências dos estudantes de medicina em um condomínio de idosos através da visita domiciliar, além de reconhecer as principais necessidades em saúde, fazer intervenções educacionais com ênfase na saúde, a fim de garantir a atenção e cuidado integral ao idoso. Trata-se de um estudo descritivo, qualitativo, com abordagem direta e observacional na modalidade Relato de Experiência. O registro de dados ocorreu por meio de fontes escritas, orais e imagéticas, no período de setembro e outubro de 2019. O idoso tem particularidades que impactam a qualidade de vida, visto que possuem maiores índices de doenças crônicas e fragilidades, mais custos para a saúde, menos recursos sociais e financeiros. Envelhecer, sem a devida assistência é um desafio. Com tantas condições desafiadoras, faz-se indispensável aproximar-se do cuidado do idoso por meio das visitas domiciliares. Assim, foi possível planejar atividades que envolvessem a coletividade, destacou-se a importância dos idosos se relacionarem e dialogar mais entre si. A visita domiciliar proporcionou benefícios mútuos. É imprescindível a ampliação da proteção social da pessoa idosa, a fim de garantir a qualidade de vida e um envelhecimento saudável. Não menos importante é a necessidade da construção do vínculo, visto que se torna mais fácil desenvolver um trabalho que contemple, ao máximo, a necessidade de quem carece do cuidado

Seasonal Variability of Atmospheric Dust Over Cape Verde Islands.

International Congresso on Environmental Health (ICEH 2012). Lisboa, 29 Maio – 1 Junho

Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

This is the published version. Copyright 2003 American Society for Microbiology.The cellular immunogenicity of formulated plasmid DNA and replication-defective human adenovirus serotype 5 (Ad5) vaccine vectors expressing a codon-optimized human immunodeficiency virus type 1 gag gene was examined in baboons. The Ad5 vaccine was capable of inducing consistently strong, long-lived CD8+-biased T-cell responses and in vitro cytotoxic activities. The DNA vaccine-elicited immune responses were weaker than those elicited by the Ad5 vaccine and highly variable; formulation with chemical adjuvants led to moderate increases in the levels of Gag-specific T cells. Increasing the DNA-primed responses with booster doses of either Ad5 or modified vaccinia virus Ankara vaccines suggests a difference in the relative levels of cytotoxic and helper responses. The implications of these results are discussed

Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study

T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a match or near-match between the epitope induced by vaccination and the infecting viral strain. We compared the frequency and specificity of the CTL epitope responses elicited by the replication-defective Ad5 gag/pol/nef vaccine used in the Step trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. Among vaccinees with detectable 15-mer peptide pool ELISpot responses, there was a median of four (one Gag, one Nef and two Pol) CD8 epitopes per vaccinee detected by 9-mer peptide ELISpot assay. Importantly, frequency analysis of the mapped epitopes indicated that there was a significant skewing of the T cell response; variable epitopes were detected more frequently than would be expected from an unbiased sampling of the vaccine sequences. Correspondingly, the most highly conserved epitopes in Gag, Pol, and Nef (defined by presence in >80% of sequences currently in the Los Alamos database www.hiv.lanl.gov) were detected at a lower frequency than unbiased sampling, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking of these responses. This may be a generic mechanism used by the virus in both contexts to escape effective T cell immune surveillance. The disappointing results of the Step trial raise the bar for future HIV vaccine candidates. This report highlights the bias towards less-conserved epitopes present in the same vaccine used in the Step trial. Development of vaccine strategies that can elicit a greater breadth of responses, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines against HIV-1