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1.
PLoS One ; 16(12): e0256885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972105

RESUMO

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06-1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.


Assuntos
Vacinas contra a AIDS/sangue , Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos/farmacologia , Formação de Anticorpos/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Criança , Regiões Determinantes de Complementaridade , Epitopos/imunologia , Humanos , Imunização , Cadeias Pesadas de Imunoglobulinas/metabolismo , Memória Imunológica/efeitos dos fármacos , Macaca mulatta , Hipermutação Somática de Imunoglobulina , Receptores Toll-Like/agonistas , Receptores Toll-Like/metabolismo
2.
Nat Commun ; 11(1): 3195, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581216

RESUMO

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 µg ml-1 correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Anti-HIV/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/imunologia , Vacinas contra a AIDS/sangue , Animais , Anticorpos Amplamente Neutralizantes/sangue , Modelos Animais de Doenças , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Meia-Vida , Imunização Passiva , Macaca mulatta , Masculino , Pênis/imunologia , Pênis/virologia , Profilaxia Pré-Exposição , Vagina/imunologia , Vagina/virologia
3.
Vaccine ; 38(3): 411-415, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31761501

RESUMO

The potential advantages and unique challenges of the early life immune system for the development of HIV-specific broadly neutralizing antibodies were discussed during a workshop entitled "Immunological Mechanisms of Inducing HIV Immunity in Infants" sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) in conjunction with the 2018 HIVR4P Conference held in Madrid, Spain. A safe and effective HIV vaccine remains a critical need in the fight against the HIV pandemic, especially to prevent emerging infections in infants, adolescents, and young adults. To successfully target these populations, a vaccine should ideally induce protective immune responses during childhood. Interestingly, several recent studies highlighting differences in immune responses between adults and children have suggested that the early life immune system could present advantages for the elicitation of broadly neutralizing antibodies (bnAbs), a response highly desired for an HIV vaccine. Notably, HIV-infected children develop bnAbs responses earlier and more frequently than infected adults; with emerging evidence that the pathways of elicitation of bnAb lineages may differ between adults and children. Moreover, there is precedent for the prevention of lifelong infections with pediatric immunization, and early life provides a unique window of opportunity for the administration of a multi-dose HIV vaccine that will likely be needed to achieve protective immunity. Further understanding of how the distinct early life immune system can be harnessed to trigger bnAb lineages for induction of durable and polyfunctional HIV-specific immunity is warranted. This strategy will include testing promising HIV vaccine candidates in pediatric populations in preclinical and clinical studies. Novel approaches to identify molecular markers of protection are also key to guide and accelerate pediatric HIV vaccine development.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/imunologia , Educação/tendências , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/sangue , Anticorpos Neutralizantes/sangue , Educação/métodos , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/prevenção & controle , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Imunização/métodos , Imunização/tendências , Lactente , Recém-Nascido
4.
PLoS One ; 14(4): e0213409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30969970

RESUMO

A major challenge in HIV vaccine development is the identification of immunogens able to elicit broadly neutralizing antibodies (bNAbs). While remarkable progress has been made in the isolation and characterization of bNAbs, the epitopes they recognize appear to be poorly immunogenic. Thus, none of the candidate vaccines developed to date has induced satisfactory levels of neutralizing antibodies to the HIV envelope protein (Env). One approach to the problem of poor immunogenicity is to build vaccines based on envelope (env) genes retrieved from rare individuals termed elite neutralizers (ENs) who at one time possessed specific sequences that stimulated the formation of bNAbs. Env proteins selected from these individuals could possess uncommon, yet to be defined, structural features that enhance the immunogenicity of epitopes recognized by bNAbs. Here we describe the recovery of envs from an EN that developed unusually broad and potent bNAbs. As longitudinal specimens were not available, we combined plasma and provirus sequences acquired from a single time-point to infer a phylogenetic tree. Combining ancestral reconstruction data with virus neutralization data allowed us to sift through the myriad of virus quasi-species that evolved in this individual to identify envelope sequences from the nodes that appeared to define the transition from neutralization sensitive envs to the neutralization resistant envs that occur in EN plasma. Synthetic genes from these nodes were functional in infectivity assays and sensitive to neutralization by bNAbs, and may provide a novel source of immunogens for HIV vaccine development.


Assuntos
Vacinas contra a AIDS/genética , Anticorpos Amplamente Neutralizantes/genética , Infecções por HIV/imunologia , HIV/imunologia , Vacinas contra a AIDS/sangue , Vacinas contra a AIDS/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Epitopos/genética , Epitopos/imunologia , HIV/genética , HIV/patogenicidade , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/genética , Anticorpos Anti-HIV/imunologia , Antígenos HIV/sangue , Antígenos HIV/genética , Antígenos HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Imunogenicidade da Vacina/genética , Testes de Neutralização , Filogenia , Provírus/genética , Provírus/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana
5.
Biomed Res Int ; 2013: 493128, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24371825

RESUMO

BACKGROUND: The number of new HIV infections among MSM of China is rapidly increasing in recent years and behavioral interventions have had limited effectiveness. To control the HIV pandemic may lie in an HIV vaccine. This study examined the factors associated with willingness to participate (WTP) in HIV vaccine clinical trials among China MSM. METHODS: A cross-sectional survey was carried out among MSM from three cities in northeast China. Questionnaires pertaining to MSM risk behavior and WTP in HIV vaccine trials were administered through computer assisted self-interviewing (CASI). RESULTS: A total of 626 MSM participated in this survey. 54.8% had occasional male partners and 52.2% always used condoms with male sex partners. HIV prevalence was 5.0%. 76.7% were WTP in a preventive HIV vaccine clinical trial. Results showed that HIV vaccination is a means of protection for spouses and family; family support to participate in vaccine trials and desire for economic incentives were significantly associated with WTP. CONCLUSIONS: There was a high proportion of WTP in HIV vaccine trials among Chinese MSM. The high HIV prevalence and high proportion of risky sexual behavior indicate that Liaoning MSM are potential candidates for HIV vaccine trials.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Inquéritos e Questionários , Vacinas contra a AIDS/sangue , Vacinas contra a AIDS/imunologia , Adulto , China , Ensaios Clínicos como Assunto , Estudos Transversais , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Comportamento Sexual , Adulto Jovem
6.
AIDS ; 25(2): 153-8, 2011 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-21150554

RESUMO

BACKGROUND: adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition. METHODS: we performed a nested case-control study of Ad5 serostatus among 299 HIV-infected and 590 matched HIV-uninfected persons participating in the Multicenter AIDS Cohort Study (MACS) and in HPTN 039, a study of herpes simplex virus 2 suppression among adults in the United States, South America, and Africa. Appropriate HIV cases and controls were identified in each cohort, and Ad5-neutralizing antibody titers were compared in these two groups. RESULTS: in MACS and HPTN 039, the relative risks of incident HIV infection among Ad5-seropositive vs. Ad5-seronegative individuals were 1.1 (95% confidence interval 0.8-1.5, P = 0.57) and 1.0 (95% confidence interval 0.4-2.3, P = 0.99), respectively. HIV-1 acquisition rates did not vary significantly by Ad5-neutralizing antibody titer. CONCLUSION: the presence of Ad5-neutralizing antibodies is not linked to the risk of HIV acquisition among populations at elevated risk of HIV infection.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por Adenoviridae/imunologia , Adenovírus Humanos/imunologia , Anticorpos Neutralizantes/imunologia , Soropositividade para HIV/imunologia , HIV-1/patogenicidade , Vacinas contra a AIDS/sangue , Infecções por Adenoviridae/sangue , Infecções por Adenoviridae/genética , Adenovírus Humanos/genética , Adulto , África , Anticorpos Neutralizantes/sangue , Estudos de Casos e Controles , Feminino , Vetores Genéticos , Humanos , Masculino , Medição de Risco , América do Sul , Estados Unidos
7.
J Acquir Immune Defic Syndr ; 46(2): 222-30, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17693888

RESUMO

BACKGROUND: The first multicenter, international National Institutes of Allergy and Infectious Diseases (NIAID)-sponsored HIV vaccine trial took place in Brazil, Haiti, Peru and Trinidad. This randomized, double-blind, placebo-controlled, phase 2 trial evaluated the safety and immunogenicity of a clade B-derived, live canarypox HIV vaccine, vCP1452. vCP1452 was administered alone or with a heterologous boost of MN rgp120 glycoprotein. The trial was pivotal in deciding whether these vaccines advanced to phase 3 efficacy trials. METHODS: Forty seronegative volunteers per site were randomized to ALVAC alone, ALVAC plus MN rgp120, or placebo in a 0, 1, 3, and 6 month schedule. Immunogenicity was assayed by chromium-release cytotoxic T lymphocyte (CTL) responses; interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays (ELISpot); lymphocyte proliferation assays (LPA); neutralization; and enzyme-linked immunosorbent assays (ELISA). RESULTS: Enrollment and follow-up were excellent. Both vaccines were well tolerated. Neutralizing antibody to the laboratory-adapted MN strain was detected. Cellular immune responses, as measured by CTL, ELISpot, and LPA, did not differ between vaccines and placebos. CONCLUSIONS: The observation of disappointing immunogenicity in this and a parallel domestic study has informed future vaccine development. Equally important, challenges to doing an integrated trial across countries, cultures, languages, and differing at-risk populations were overcome. The identification of specific safety, ethical, logistic, and immunological issues in this trial established the foundation for current larger international studies.


Assuntos
Vacinas contra a AIDS/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1 , Vacinação , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/sangue , Adolescente , Adulto , Brasil , Método Duplo-Cego , Feminino , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/administração & dosagem , Proteína gp120 do Envelope de HIV/sangue , Haiti , Humanos , Esquemas de Imunização , Imunização Secundária , Injeções Intramusculares , Interferon gama/análise , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Peru , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Trinidad e Tobago , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/sangue , Vacinas Sintéticas/imunologia
9.
BMC Infect Dis ; 2: 19, 2002 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-12223114

RESUMO

BACKGROUND: It has not been clearly demonstrated whether HIV vaccination can complicate routine HIV testing. In this report, we describe the laboratory data of two prisoners who received rgp120 vaccine in a phase III trial underway in Thailand. These data indicate that previous vaccination may complicate the interpretation of screening HIV diagnostic tests. CASE PRESENTATION: The participants were identified from a cohort study on "Health factors related to HIV-1 and other viral infections among incarcerated people" that was approved by The Ethical Committee for Research in Human Subjects, Ministry of Public Health, Thailand. HIV diagnosis was definitively established with serial specimens using multi-screening tests, Western blot and diagnostic PCR.Anti-HIV screening tests consistently exhibited either weakly reactive or inconclusive results. The band patterns of the Western blot analysis corresponded to those found in individuals who received the rgp120 vaccination. Definite results were established using diagnostic PCR, which exhibited consistently negative results with follow-up specimens. Such problems in HIV testing are not easily resolved in the routine clinical setting in Thailand. CONCLUSIONS: These data demonstrate that HIV-1 vaccination interferes with routine diagnostic tests. Similar cases will not be uncommon in Thailand, where 2,545 people have already participated in a phase III trial.


Assuntos
Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/sangue , Sorodiagnóstico da AIDS/métodos , Vacinas contra a AIDS/uso terapêutico , Ensaios Clínicos Fase III como Assunto/efeitos adversos , Proteína gp120 do Envelope de HIV/sangue , Proteína gp120 do Envelope de HIV/uso terapêutico , Proteína gp160 do Envelope de HIV/sangue , Infecções por HIV/epidemiologia , HIV-1/imunologia , HIV-1/isolamento & purificação , Dependência de Heroína/sangue , Humanos , Masculino , Programas de Rastreamento/métodos , Uso Comum de Agulhas e Seringas/efeitos adversos , Prisioneiros , Estudos Retrospectivos , Tailândia/epidemiologia
10.
Clin Diagn Lab Immunol ; 2(3): 268-71, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7664169

RESUMO

There is a need for human immunodeficiency virus (HIV) screening assays which will distinguish uninfected HIV vaccine recipients from HIV-infected individuals. Commercial screening kits were used to test serum samples from low- and high-risk participants in clinical trials before and after immunization with various recombinant HIV type 1 (HIV-1) envelope glycoprotein 120 (gp120) candidate vaccines. All kits were 100% sensitive in detecting HIV infection. Both Murex Single Use Diagnostic System and United Biomedical, Inc., HIV type 1 or 2 (HIV-1/2) enzyme immunoassay (EIA) kits, which detect antibodies to HIV-1 gp41, were 98 to 100% specific when used to screen baseline or recombinant gp120-vaccinated populations as vaccine-induced antibodies to gp120 were nonreactive in these tests. The Abbott HIVAB HIV-1 EIA (lysate of whole infected cells, reactive with anti-gp120 antibodies) gave high levels of reactivity due to vaccine-induced antibodies and a high baseline rate of false positives (12 of 83) among nonvaccinated high-risk volunteers. Assays containing only gp41 and p24 solid-phase components are compatible with gp120-based vaccines but are unlikely to be useful in a similar role for vaccines containing gp160, gp41, or gp120 plus p24 antigens. Efficacy trials must be designed in concert with available diagnostic screening assays to avoid problems caused by vaccine-induced seroconversion in high-risk populations.


Assuntos
Vacinas contra a AIDS/sangue , Síndrome da Imunodeficiência Adquirida/diagnóstico , HIV-1/imunologia , Kit de Reagentes para Diagnóstico , Vacinas contra a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Anticorpos Anti-HIV/sangue , Antígenos HIV/sangue , Humanos , Estudos Soroepidemiológicos
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