Exploring a community's understanding of HIV vaccine-induced seropositivity in a South African research setting

Background. The high HIV prevalence and incidence in South Africa makes it suitable for recruitment of participants for large-scale HIV preventive vaccine trials. However, fear of vaccine-induced seropositivity (VISP) may be a barrier for community acceptability of the trial, for volunteers to participate in HIV preventive vaccine trials and for uptake of an efficacious vaccine. Prior to 2015, when the first phase 1 safety HIV vaccine trial was undertaken at Setshaba Research Centre, Soshanguve, the local community stakeholders and healthcare workers were naive about HIV vaccine research and HIV preventive vaccines. Objective. To explore knowledge and perceptions regarding VISP among community stakeholders and healthcare workers in peri-urban Soshanguve, Tshwane.Methods. Using a quantitative-qualitative mixed-methods study design, surveys (n=50) and in-depth interviews (n=18) were conducted during July - August 2015. Participants included community stakeholders, community advisory board members and healthcare workers, who were >18 years old and had attended community educational workshops during September 2014 - May 2015. Audio recordings of interviews were transcribed verbatim and coded using content thematic analysis. Data were further analysed by sex, age and educational level.Results. Of a maximum score of 2 on knowledge on VISP, the 50 survey participants (mean age 33.78 years; 45 females) obtained an average of 0.88 (44%). Of 17 in-depth interviewees (one interview could not be transcribed; mean age 30.9 years; 12 females), 8 (47%) displayed some knowledge about VISP, of whom only 5 defined VISP correctly. Women were more knowledgeable about VISP than men; 5 of 12 women (42%) came close to defining VISP correctly, while none of the 5 men did so. The main fear of trial participation expressed by most participants (n=6) was testing HIV-positive as a result of the vaccine. While some participants believed that the community's perceptions of VISP would negatively affect HIV vaccine trial support and recruitment efforts, others noted that if trial participants understand the concept of VISP and are part of support groups, then they would have the information to combat negative attitudes within their community. Conclusion. Most participants had an inaccurate and incomplete understanding of VISP. Many feared testing HIV-positive at clinics; therefore, education on improving a basic understanding of how vaccines work and why VISP occurs is essential. In addition, assessing participant understanding of HIV testing, transmission and VISP is critical for recruitment of participants into HIV vaccine trials and may improve acceptability of an HIV preventive vaccine

Developing capacity for implementation and evaluation of vaccine trials in Uganda: Perspective of the Makerere University Walter Reed Project

Introduction: Infectious diseases and neglected tropical diseases continue to be a major challenge in resource limited settings, causing significant morbidity and mortality. Although vaccines are a key biomedical prevention tool, resource limited settings often lack the infrastructure, regulatory frameworks, and skilled human resource to conduct vaccine clinical trials. To address this gap, the Makerere University Walter Reed Project (MUWRP) was established and has contributed to vaccine research in Uganda and globally. Methods: This was achieved through training a strong vaccine clinical trial workforce; development of requisite clinical trial infrastructure for research activities and management of investigational products; conducting phase I-III vaccine trials and contribution to national ethical and regulatory frameworks that protect participants. Results: As of 2022, MUWRP had successfully conducted and completed five phase I/II HIV vaccine clinical trials, five for Ebola and Marburg, while one phase I/II Schistosomiasis and one phase III COVID-19 vaccine clinical trial are ongoing. Discussion: The completed vaccine trials provided critical scientific knowledge on the safety and immunogenicity of investigational products which informed the design of better vaccines for diseases of global health importance. Conclusion: Academia, through establishment of appropriate partnerships can contribute to the identification of solutions to complex public health challenges

Construção, caracterização biológica e imunológica de vírus recombinante de vírus vacinal da febre amarela 17d, que expressam o fator de infectividade viral (vif) do vírus da imunodeficiência símia sivmac239 / Construction, biological and immunological characterization of 17d yellow fever vaccine virus recombinant virus, which express the viral infectivity factor (vif) of the simian immunodeficiency virus sivmac239

O desenvolvimento de uma vacina segura e eficiente contra o HIV é considerada uma ótima medida/estratégia para controlar a epidemia mundial do HIV. Este projeto visou construir e avaliar a imunogenicidade dos vírus da febre amarela recombinante da vacina 17D que expressam antígenos do fator de infectividade viral (Vif) do vírus da imunodeficiência símia SIVmac239. O vírus da vacina da febre amarela 17D tem sido usado como vetor de protótipos de vacinas por ser um imunógeno robusto e seguro. Nosso objetivo foi avaliar vírus recombinantes da febre amarela 17D que carreiam fragmentos de genes Vif (HIV/SIV), e que foram construídos com a tecnologia do clone infeccioso e a inserção do gene de Vif na região intergênica E/NS1 do genoma do vírus vacinal da febre amarela 17D. Verificamos anteriormente que o vírus recombinante FA/Vif 1-110 original era geneticamente instável, perdendo completamente o fragmento Vif 1-110 até à quinta passagem em série em células Vero. Nós alcançamos a estabilidade genética quando deletamos a região N-terminal de Vif, que provavelmente estava interferindo na replicação do vírus da FA 17D. Chamamos de FA/Vif 42-110, o vírus que sofreu a deleção do N-terminal, e que é geneticamente estável. Mas também construímos o FA/Vif 1-110 variante, que possui o mesmo fragmento do FA/Vif 1-110 original, porém é mais estável devido as mudanças realizadas na plataforma de expressão da proteína heteróloga. Incluímos nas primeiras investigações de imunogenicidade, o FA/Vif 102-214 construído anteriormente. Nós hipotetizamos que a estabilidade genética viral poderia aumentar a imunogenicidade viral

Assim, realizamos duas imunizações em camundongos C57BL/6 com os vírus FA/Vif para a avaliação da imunogenicidade em relação à formação de células T de memória contra o vírus da FA e Vif, e indução de anticorpos neutralizantes contra o vírus da FA, gerados pelas imunizações. O vírus FA/Vif 1-110 variante e o FA/Vif 42-110 se apresentaram como bons indutores de resposta celular, porém o FA/Vif 42-110 apresentou a menor média de título de anticorpos neutralizantes. O vírus FA/Vif 102-214 apresentou bons resultados de resposta imune celular e humoral, apesar de não ter sido avaliado dentro da resposta imune celular específica. O vírus FA/Vif 1-110 variante conseguiu uma boa indução da resposta celular e humoral, e o vírus FA/Vif 1-110 original parece promissor segundo os nossos dados de resposta celular de memória efetora, apesar de ter apresentado uma média baixa de títulos de anticorpos neutralizantes. De maneira geral, os vírus FA/Vif induzem diferentes braços de resposta imune, sendo uns mais indutores de resposta celular que humoral e vice-versa. Com os vírus FA/Vif apresentando essas características em relação a resposta imune, não conseguimos relacionar a estabilidade genética com imunogenicidade, mas uma estratégia promissora para abranger os dois tipos de resposta, seria o uso de formulações virais, utilizando dois ou mais vírus FA/Vif no regime vacinal. (AU)

The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects

A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.

Advances in the Immunogenic Design of HIV-1 Vaccine / 病毒学报

A safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is expected to have a considerable impact on elimination of acquired immune deficiency syndrome. Despite decades of effort, an effective vaccine against HIV-1 remains elusive. In recent years, the Thai HIV Vaccine Efficacy Trial (known as RV144) showed a reduction in HIV-1 acquisition by 31%, but this agent could not delay disease progression in vaccinated individuals. Clinical analyses of experimental data and experiments in vitro have revealed two main types of immunogen design: induction of broad-spectrum neutralizing antibody (bNAb) and cytotoxic T lymphocyte (CTL) responses. bNAb can prevent or reduce acquisition of infection, and its main immunogens are virus-like particles, natural envelope trimers and stable bNAb epitopes. An effective CTL response can slow-down viral infection, and its main immunogens are "mosaic" vaccines, "conserved immunogens", and the "fitness landscape" of HIV-1 proteins. This review summarizes the strategies as well as progress in the design and testing of HIV-1 immunogens to elicit bNAb and CTL responses.

Study on Cellular Immune Responses of DNA Vaccine, rAd5 and rMVA Expressing SIV Gag/Env Gene Combined Immunization in Mice / 病毒学报

Therapeutic HIV vaccine was considered as a hopeful curative method for AIDS patients. However, there is still no suitable HIV animal model for vaccine study since the difference in the immune system between human and animals. To evaluate the therapeutic effect of combined immunization strategy with multiple vector vaccines in macaque models. Plasmid DNA, recombinant Ad5 and MVA vaccines which expressing SIV gag and env genes were constructed. Sequential and repeated immune strategy were applied to immunize mice with these three vaccines. Cellular immune responses in mice immunized with these three vaccines were measured by ELISPOT test in vitro and CTL assay in vivo. The results were analyzed and compared with different antigen combination, order of vaccines and intervals to choose a suitable immunization strategy for macaque immunization in future. It indicated that strong SIV-Gag/Env-specific cellular immune responses were induced by these three vector vaccines. It laid a foundation for evaluating the therapeutic effect of combined immunization strategy with multiple vector vaccines in SIV infected macaque models.

Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.

Attracting; Equipping and Retaining Young Medical Doctors in HIV Vaccine Science in South Africa

Background: HIV remains a significant health problem in South Africa (SA). The development of a preventive vaccine offers promise as a means of addressing the epidemic; yet development of the human resource capacity to facilitate such research in SA is not being sustained. The HIV Vaccine Trials Network (HVTN) has responded by establishing South African/HVTN AIDS Early Stage Investigator Programme (SHAPe); a programme to identify; train and retain clinician scientists in HIV vaccine research in SA.Objectives: The present study sought to identify factors influencing the attraction and retention of South African medical doctors in HIV vaccine research; to understand the support needed to ensure their success; and to inform further development of clinician research programmes; including SHAPe.Methods: Individual interviews and focus groups were held and audio-recorded with 18 senior and junior research investigators; and medical doctors not involved in research. Recordings were transcribed; and data were coded and analysed.Results: Findings highlighted the need for: (1) medical training programmes to include a greater focus on fostering interest and developing research skills; (2) a more clearly defined career pathway for individuals interested in clinical research; (3) an increase in programmes that coordinate and fund research; training and mentorship opportunities and (4) access to academic resources such as courses and libraries. Unstable funding sources and inadequate local funding support were identified as barriers to promoting HIV research careers.Conclusion: Expanding programmes that provide young investigators with funded research opportunities; mentoring; targeted training and professional development may help to build and sustain SA's next generation of HIV vaccine and prevention scientists

A novel immunization strategy to induce strong humoral responses against HIV-1 using combined DNA, recombinant vaccinia virus and protein vaccines / 病毒学报

To optimize the immunization strategy against HIV-1, a DNA vaccine was combined with a recombinant vaccinia virus (rTV) vaccine and a protein vaccine. Immune responses against HIV-1 were detected in 30 female guinea pigs divided into six groups. Three groups of guinea pigs were primed with HIV-1 DNA vaccine three times, boosted with rTV at week 14, and then boosted with gp140 protein at intervals of 4, 8 or 12 weeks. Simultaneously, the other three groups of animals were primed with rTV vaccine once, and then boosted with gp140 after 4, 8 or 12 weeks. The HIV-1 specific binding antibody and neutralizing antibody, in addition to the relative affinity of these antibodies, were detected at different time points after the final administration of vaccine in each group. The DNA-rTV-gp140 immune regimen induced higher titers and affinity levels of HIV-1 gp120/gp140 antibodies and stronger V1V2-gp70 antibodies than the rTV-gp140 regimen. In the guinea pigs that underwent the DNA-rTV-gp140 regimen, the highest V1V2-gp70 antibody was induced in the 12-week-interval group. However, the avidity of antibodies was improved in the 4-week-interval group. Using the rTV-gp140 immunization strategy, guinea pigs boosted at 8 or 12 weeks after rTV priming elicited stronger humoral responses than those boosted at 4 weeks after priming. In conclusion, this study shows that the immunization strategy of HIV-1 DNA vaccine priming, followed by rTV and protein vaccine boosting, could strengthen the humoral response against HIV-1. Longer intervals were better to induce V1V2-gp70-specific antibodies, while shorter intervals were more beneficial to enhance the avidity of antibodies.

Formulação vacinal trivalente voltada para o controle profilático/terapêutico de tumores induzidos pelo vírus do papiloma humano tipo 16 (HPV-16) e infecções pelos vírus da imunodeficiência adquirida (HIV) e herpes vírus humano (HSV) / Trivalent vaccine formulation focused on the prophylactic / therapeutic control of tumors induced by human papillomavirus type 16 (HPV-16) and infection by human immunodeficiency virus (HIV) and human herpes virus (HSV)

As proteínas E7 (HPV), p24 (HIV) e gD (HSV) são exclusivamente expressas por células infectadas ou tumorais e, por isso, são utilizadas como alvos para vacinas com características terapêuticas. Foram desenvolvidas duas vacinas de DNA capazes de expressar as três proteínas virais por meio de um vetor de expressão bicistrônico baseado na sequência IRES. As vacinas, denominadas pIRES I e pIRES II, diferem entre si por transportarem os genes que codificam as proteínas E7 do HPV-16 e p24 do HIV fusionadas à proteína gD do HSV-1 em ordem inversa. Células COS-7 transfectadas com os plasmídeos vacinais expressaram as proteínas alvo, como determinado por imunofluorecência com anticorpos específicos para as proteínas gD, p24 e E7. As vacinas foram testadas em modelo murino quanto à capacidade de gerar anticorpos e células T CD8+ específicas. Observamos que animais vacinados desenvolveram baixas taxas de anticorpos contra gD, p24 e E7. Em contrapartida, demonstramos a indução de células T CD8+ específicas para os três antígenos testados. Os plasmídeos vacinais foram capazes de proteger camundongos inoculados com células tumorais TC-1 (que expressam a proteína E7 do HPV-16), embora apresentando diferentes níveis de proteção em ensaios profiláticos e terapêuticos. As formulações foram testadas em relação à capacidade de proteger animais frente a desafio com o HSV-1 sendo que apenas um deles gerou efeito protetor. Em conclusão, os resultados demonstram que vacinas voltadas para o controle terapêutico de infecções ou processos tumorais associados aos vírus HPV, HIV e HSV representam uma meta viável e promissora

The proteins E7 (HPV), p24 (HIV) and gD (HSV) are exclusively expressed by infected cells or tumors and therefore are used as targets for vaccines with therapeutic characteristics. We developed two DNA vaccines capable of expressing these three viral proteins using a bicistronic expression vector based on IRES sequence. The plasmid vaccines, named pIRES I and pIRES II, differ by carrying the genes that encode proteins of HPV-16 E7 and p24 fused to the HIV protein gD of HSV-1 in reverse order. Transfected COS-7 cells expressed the target proteins, as determined by immunofluorescence with specific antibodies for gD, p24 and E7. The vaccines were tested in mice for their ability to generate antibodies and specific CD8+ T cells. We observed that vaccinated animals developed low levels of antibodies against gD, E7 and p24. In contrast, we demonstrate the induction of specific CD8+ T cells for the three antigens. The plasmid vaccines were able to protect mice inoculated with TC-1 tumor cells (which express the E7 protein of HPV-16), although with different levels of protection in prophylactic and therapeutic trials. The formulations were tested for ability to protect animals against challenge with HSV-1 and only one of them generated a protective effect. In conclusion, the results show that vaccines directed to therapeutic control of infections or tumor process associated with HPV, HSV or HIV represents a promising and viable goal

Avaliação da resposta de células T frente aos peptídeos de GAG e NEF do HIV-1 e de parâmetros imunológicos e genéticos associados ao controle da replicação viral / Evaluation of t cells responses against hiv-1 gag and nef peptides and immunological and genetic parameters associated to control of viral replication

A pandemia do HIV-1 é a infecção emergente mais importante das últimas décadas. O desenvolvimento de uma vacina é colocado como a melhor estratégia para o controle da pandemia. No entanto, entre os candidatos vacinais que evoluíram para testes clínicos de eficácia, apenas um mostrou resultados positivos, mas com uma modesta eficácia (31,2 por cento). Além da busca por uma vacina eficiente contra a infecção pelo HIV-1, o desenvolvimento de estratégias para se atingir a cura também é essencial. Considerando esses dois objetivos principais, diversos fatores são colocados como obstáculos, sendo a enorme diversidade genética do HIV-1 e a falta de correlatos de proteção contra a doença ou a infecção, os pontos centrais e nos quais focamos nossa atenção. No primeiro trabalho, foi avaliada a resposta de células T frente a peptídeos derivados de sequências consensos e sequências de isolados virais mais próximos ao consenso (CVI) dos três subtipos prevalentes no Brasil,B, C e F1 e do grupo M. O estudo incluiu 32 indivíduos infectados com o HIV-1, subtipo B (n= 13), subtipo C (n = 11) e subtipo F1 (n = 8). As respostas específicas frente a Gag e Nef foram avalidas usando o ensaio de ELISpot IFN-gama. Peptídeos baseados nas sequências CVI apresentaram capacidade de redução da distância genética e de detecção da resposta de células T similar ao observado para as sequências consenso. Em geral, o nível de reatividade cruzada entre os subtipos B e F1 foi maior do que entre os subtipos B e C ou entre os subtipos C e F1. Esses resultados sugerem que o obstáculo imposto pela diversidade genética no desenho de vacinas é dependente dos subtipos envolvidos. No segundo trabalho foi avaliada a resposta de células T de indivíduos controladores da replicação viral frente aos peptídeos consenso, derivados do primeiro estudo...

Willingness to participate in future HIV prevention trials in Beira, Mozambique

In preparation for trials of new HIV prevention methods; willingness to participate (WTP) was assessed in Beira; Mozambique. A totla of 1 019 women participating in an HIV incidence study; and 97 men participating in a separate WTP survey; were interviewed. When comparing the answers to questions that were identical in the two studies; WTP was higher among women than men for all prevention methods. Among women; WTP was highest for trials evaluating daily oral pre-exposure prophylaxis (PrEP; 84.4 reporting very likely to participate); followed by vaccination (77.8); daily vaginal gel use (67.7); coital vaginal gel use (67.1) and monthly vaginal ring use (47.7). Among men; WTP was highest for trials evaluating vaccination (57.6); followed by daily vaginal gel use for female sexual partners (52.5); daily oral PrEP (49.5); coital vaginal gel use for female sexual partners (46.4) and monthly vaginal ring use for female sexual partners (39.4). Among men; the most important motivators for trial participation were social benefits; whereas personal risks (most notably receiving injections and/or blood draws) were deterrents; this was not assessed in women. Other important lessons learnt are that male circumcision and antiretroviral drugs were not generally recognised as ways to prevent HIV; that having to use hormonal contraception during trial participation will likely reduce WTP; and that evening clinics are not likely to be popular. The barriers reported in this and other studies may be challenging but are not impossible to overcome

Recruitment of Caribbean female commercial sex workers at high risk of HIV infection / Captación de mujeres profesionales del sexo con alto riesgo de infección por VIH en el Caribe

OBJECTIVE: To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean. METHODS: A prospective cohort study was conducted in 2009-2012 among 799 female commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum eligibility criteria included exchange of sex for goods, services, or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period. Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies. Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial. Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study. RESULTS: HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2, 95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated with HIV infection. A total of 88.9% of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial. CONCLUSIONS: This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial.

OBJETIVO: Evaluar nuevos criterios de selección y métodos extrainstitucionales encaminados a detectar y captar a las mujeres con alto riesgo de contraer la infección por virus de la inmunodeficiencia humana (VIH) en el Caribe. MÉTODOS: Del 2009 al 2012, se llevó a cabo un estudio prospectivo de cohortes de 799 mujeres profesionales del sexo en la República Dominicana, Haití y Puerto Rico. Los requisitos mínimos de selección fueron el intercambio de relaciones sexuales por bienes, servicios o dinero en los últimos 6 meses y las relaciones sexuales vaginales o anales sin protección con un hombre durante el mismo período. En cada centro se aplicaron criterios de selección y estrategias de captación más restrictivos, en función de las características epidemiológicas locales. Se formularon a las participantes preguntas acerca de la infección por el VIH/sida y su motivación para participar en un estudio clínico sobre la vacuna contra el VIH. Se usó un modelo de regresión logística con el fin de analizar los factores pronósticos de prevalencia de infección por el VIH y la voluntad de participar en un estudio futuro sobre la vacuna contra el virus. RESULTADOS: La prevalencia de infección por el VIH en el momento del tamizaje fue 4,6%. El consumo de crack se asoció con la infección por el VIH (razón de posibilidades [OR]: 4,2; intervalo de confianza [IC] de 95%: 1,8-9,0) y la práctica de relaciones sexuales con clientes en un hotel o un motel se asoció inversamente con esta infección (OR: 0,5; IC 95%: 0,3-1,0). El 88,9% de las mujeres inscritas manifestó una disposición decidida o probable de participar en un estudio futuro sobre la vacuna contra el VIH. CONCLUSIONES: Los resultados del estudio indican que es posible formular criterios de selección e introducir métodos de captación locales con el propósito de detectar y captar a las mujeres profesionales del sexo, que presentan una prevalencia de infección por el VIH mayor que la población general y manifiestan una buena disposición de participar en un ensayo clínico sobre la vacuna contra el VIH.

Eventos adversos supuestamente atribuibles a la vacunación e inmunización en hijos de madres infectadas con el virus de la inmunodeficiencia humana / Supposedly attributable to vaccination and immunization in children of mothers infected with human immunodeficiency virus adverse events

Introducción: las vacunas son una de las intervenciones sanitarias más importantes y difundidas. La monitorización de su seguridad a través del registro de eventos adversos es imprescindible. Los hijos de madre infectada por el virus de la inmunodeficiencia humana (VIH), expuestos,infectados o serorrevertidos son un grupo particular de individuos dentro del esquema de inmunización. El objetivo del presente estudio fue describir la frecuencia de eventos adversos supuestamente atribuibles a la vacunación e inmunización (ESAVI) en los hijos de madres infectadas con VIH. Metodología: se realizó un estudio descriptivo, de corte transversal entre el 1º de setiembre de 2008 y el 28 de febrero de 2011 en el Centro Nacional de Referencia Obstétrico-Pediátrico VIH-SIDA del Centro Hospitalario Pereira Rossell con los pacientes allí controlados ( infectados y no infectados) que requerían vacunación en sus controles. Se registró el porcentaje y tipo de eventos producidos. Resultados: de 189 pacientes, 110 (58%) entregaron el formulario con un total de 157 registros. La mediana de edad fue de 2 meses (rango de 2 meses a 17 años). El 63% era menor de 6 meses. De los 110 niños, 34 eran infectados y 76 no infectados. Se registraron eventos adversos en 49 (44,5%) pacientes. Hubo 108 eventos leves y 23 graves. El porcentaje de ESAVI en ambos grupos fue similar (p>0,05). No se registraron hospitalizaciones ni eventos difíciles de catalogar como relacionados a vacunación. Conclusiones: las vacunas administradas en eseperíodo fueron seguras con similares ESAVI en ambos grupos de pacientes. Continuar vigilando la aparición de ESAVI y comparar los resultados año a año será importante para actualizar recomendaciones y garantizar la seguridad de los pacientes y sus cuidadores.

The application of recombinant Bacillus Calmette-Guérin vaccine and its vector in infectious disease / 生物医学工程学杂志

Recent studies show that the vector of recombinant Bacillus Calmette-Guérin (rBCG) has a series of advantages. With exogenous gene and vaccine in one inoculation, it can obtain strong and persistent immune response at one time so that BCG is considered as a kind of ideal vector for live recombinant vaccine. This review outlines the application of rBCG vaccine and its vector in infectious diseases caused by bacteria, viruses, other microorganisms and parasites.

Closing the door to human immunodeficiency virus

The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention.

Perspectivas de curación: DermaVir, una vacuna de ADN con efecto terapéutico contra el VIH/sida y desarrollada racionalmente / Towards a cure: DermaVir, a rationally designed therapeutic DNA vaccine against HIV/AIDS

Hallazgos recientes en el área de la intensificación de los tratamientos antirretrovirales demuestran que la forma de llegar a una curación para el VIH exige la inclusión de nuevas estrategias de tratamiento como las vacunas terapéuticas. La vacuna terapéutica DermaVir incluye elementos tecnológicos clave en el diseño de una vacuna racional: un único inmunógeno plásmido de ADN (pADN) que expresa a 15 antígenos del VIH, formulación de nanomedicina y una única administración tópica de la vacuna enfocada a las células dendríticas. Luego de su administración tópica sobre la piel preparada, las células epidérmicas de Langerhans activadas transportan la nanomedicina DermaVir a los nódulos linfáticos para expresar a los antígenos del VIH codificados como pADN e inducir a las células T precursoras/de memoria con una alta capacidad de proliferación. Se han demostrdo la seguridad, la inmunogenicidad y la eficacia preliminar de la DermaVir en varios modelos animales y en humanos con infección por VIH. Esta novedosa tecnología de vacunación terapéutica podría constituir un nuevo paradigma en el trtamiento contra el VIH.

Recent findings on the field of antiretroviral treatment intesnsification demonstrate thar the way towards a cure for HIV requires the involvement of novel treatment strategies like therapeutic vaccines. DermaVir therapeutic vaccine includes key technological elements of rational vaccine design: a single plasmid DNA (pDNA) immunogen that expresses 15 HIV antigens, nanomedicine formulation and a unique dendritic cell-targeting topical vaccine administration. Following topical administration on the prepared skin, DermaVir nanomedicine is transported by activated epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity. Safety, immunogenicity and preliminary efficacy of DermaVir have been demonstrated in several animal models and HIV-infected human subjects. This novel therapeutic vaccination technology might offer a new treatment paradigm against HIV.

Immunogenicities and comparison of DNA vaccines encoding pol genes derived from B`/C and A/E recombinant HIV-1 strains / 中华预防医学杂志

<p><b>OBJECTIVE</b>To construct and compare the immunogenicities of DNA vaccines expressing pol genes derived from B`/C and A/E recombinant subtypes of HIV-1 in China.</p><p><b>METHODS</b>Two DNA vaccines were constructed by inserting the codon optimized pol genes derived from B'/C and A/E subtypes of HIV-1 into mammalian expression vector pSV1.0. In vitro expression efficiencies of the two DNA vaccines were determined by Western blotting and their immunogenicities were compared by i.m. immunizing female BALB/c mice. After immunization, mice splenocytes were isolated sterilely and IFN-γ based enzyme linked immunospot assay (ELISPOT) was employed to read out the specific T cell immunity.</p><p><b>RESULTS</b>The constructed DNA vaccines were validated by restriction enzyme digestion and DNA sequencing. Western blotting result showed both of the two DNA vaccines could be expressed at appreciable levels in vitro. Under the stimulation of Consensus B Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (636±178) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (468±265)SFCs/10(6) splenocytes (P=0.412). Under the stimulation of HIV-1 AE2f Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (1378±611) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (713±61) SFCs/10(6) splenocytes (P=0.134). Further analysis suggested pSVAE-Pol induced specific T cell responses mainly focused on Pol 1 peptide pool, while, in addition to induce Pol 1 specific T cell responses, pSVCN-Pol could also elicit T cell responses against consensus B Pol 2 peptide pool.</p><p><b>CONCLUSION</b>Although pSVAE-Pol was more immunogenic, pSVCN-Pol could induce T cell responses against broader epitope spectrum. Rational vaccine design may need combine them together.</p>

Cloning, expression, purification and immunoreactivity analysis of gag derived protein p17 from HIV-1 CRF35 in fusion with thioredoxin from human subjects

So far, recombinant antigens of HIV-1, the etiologic cause of Acquired Immunodeficiency Syndrome [AIDS], have been widely used for the diagnosis and vaccine development. P17 or the matrix protein formed by the proteolytic cleavage of gag is strongly antigenic and is as conserved and immunogenic as p24. In some cases, antibodies to p17 are more prevalent than antibodies to p24 and the decline in the level of p17 antibodies is an earlier prognostic marker for disease progression than decline in the level of antibodies to p24. The aim of this study was to clone and express the gag derived p17 protein in soluble form in E. coli and then assess the immunoreactivity of produced recombinant p17. DNA sequence encoding p17 matrix protein was cloned from PTZ-gag53-IR vector that has the complete gag polyprotein sequence. The T7-promoter-based expression system used in this study was TOPO directional cloning strategy that expressed p17 matrix protein in fusion with thioredoxin in E. Coli. Purification of produced recombinant protein has been done using Ni-NTA nickel chelating agarose beads. Sequencing result of the cloned sequence showed that it belongs to CRF35_AD subtype of HIV-1 which is highly prevalent in Iran and Afghanistan. The immunoreactivity of produced recombinant p17 to sera from infected individuals showed 93.8% sensitivity and 100% specificity