RESUMEN
Eleven HIV-1 seronegative subjects previously injected with an HIV-1 p17 synthetic peptide vaccine (HGP-30) were given two booster immunizations to evaluate memory cell responses and the ability to boost cellular and humoral immune responses. Five of 11 subjects showed a significant increase in their antibody titres to HGP-30 or p17 and 6/11 had T-cell proliferation responses to either HGP-30 or p17. HIV-1 virus challenge studies in SCID mice demonstrated that 39 of 50 mice (78%) receiving PBMC from 5 of the HGP-30 immunized subjects were protected from infection with a different strain of HIV-1 compared to 4 of 30 mice (13%) that received PBMC from 3 non-immunized subjects (p < 0.001). These studies show that booster immunizations with HGP-30 vaccine are safe and non-toxic and induce protective cell mediated immune responses.
Asunto(s)
Vacunas contra el SIDA/uso terapéutico , Antígenos VIH/inmunología , Infecciones por VIH/prevención & control , Seronegatividad para VIH/inmunología , VIH-1/inmunología , Inmunización Secundaria , Péptidos/inmunología , Vacunas contra el SIDA/inmunología , Adulto , Animales , División Celular/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Anti-VIH/sangre , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Productos del Gen gag del Virus de la Inmunodeficiencia HumanaRESUMEN
A vaccine breakthrough occurred in a phase 1 clinical trial of a human immunodeficiency virus (HIV) type 1 candidate subunit vaccine. The vaccine antigen, gp120SF2, is a fully glycosylated protein produced in mammalian cells from the HIVSF2 isolate. After 4 immunizations, the subject developed neutralizing antibodies and lymphoproliferative responses to the gp120 protein. About 18 weeks after the last immunization, the subject became HIV infected. During the acute phase of infection, there was high virus burden, a decline in CD4+ T lymphocytes, increases in rgp120SF2-binding antibodies and HIVSF2- and HIVMN-neutralizing antibodies, and transient lymphoproliferative responses to HIV-1 envelope and core proteins. The nucleotide sequence of the V3 loop from 2 virus isolations displayed close similarity to the V3 sequence of the vaccine antigen. Thus, the immunologic responses induced by the vaccine in this subject did not protect him from HIV-1 infection.
Asunto(s)
Vacunas contra el SIDA/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto , Secuencia de Aminoácidos , Recuento de Linfocito CD4 , Anticuerpos Anti-VIH/sangre , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/prevención & control , Infecciones por VIH/virología , VIH-1/genética , Homosexualidad Masculina , Humanos , Inmunidad Activa , Masculino , Datos de Secuencia Molecular , Pruebas de Neutralización , Fragmentos de Péptidos/genética , ARN Viral/sangre , ARN Viral/genética , Análisis de Secuencia de ADN , VacunaciónRESUMEN
A phase 1 study of 42 non-human immunodeficiency virus type 1 (HIV)-infected volunteers was initiated to determine the safety and immunogenicity of an HIV subunit vaccine consisting of recombinant envelope gp120 derived from HIVSF2 (rgp120SF2) combined with a novel adjuvant, MF59, with or without the immunomodulator muramyl tripeptide dipalmitoyl phosphatidylethanolamine (MTP-PE). All injections contained adjuvant MF59, and subjects were grouped according to MTP-PE dose. Injections were given on days 0, 30, 180, and 365. The vaccine was well tolerated with limited local and systemic reactions. These immunizations induced rgp120SF2-specific binding antibodies that persisted > or = 24 weeks. After three immunizations, all subjects receiving the antigen developed neutralizing antibodies to HIVSF2, and serum from 67% of these subjects also cross-neutralized HIVMN. ELISA-reactive antibodies to the HIVSF2 V3 region and strong lymphoproliferative responses to HIVSF2 envelope proteins were detected in all rgp120SF2-immunized subjects.
Asunto(s)
Vacunas contra el SIDA/inmunología , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adyuvantes Inmunológicos/administración & dosificación , Proteína gp120 de Envoltorio del VIH/inmunología , Fosfatidiletanolaminas/administración & dosificación , Polisorbatos/administración & dosificación , Escualeno/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas contra el SIDA/administración & dosificación , Acetilmuramil-Alanil-Isoglutamina/administración & dosificación , Adolescente , Adulto , Método Doble Ciego , Femenino , Anticuerpos Anti-VIH/sangre , Humanos , Inmunización , Masculino , Persona de Mediana Edad , Vacunas Sintéticas/administración & dosificaciónRESUMEN
HGP-30-KLH vaccine in alum at doses of 10, 25, 50, and 100 micrograms/kg administered intramuscularly at weeks 0, 4, and 10 appear well-tolerated clinically. Local pain at the injection site, appears to be the main clinical toxicity. Laboratory parameters are not affected by administration of the vaccine candidate except for perhaps mild urinalysis abnormalities at the highest dose. This vaccine candidate has no apparent immunotoxicity and does not appear to affect lymphocyte populations or T-cell functional studies. Low levels and transient antibodies develop in a minority of subjects early after immunization with the vaccine candidate. These responses were observed in the lowest dose range. Higher doses, and longer follow-up will be needed to confirm this observation. T-cell proliferative responses to KLH and KLH-HGP-30 are consistent and may not be dose dependent, but the proliferative responses are variable and more data need to be accumulated. Preliminary, there appears to be an HGP-30-induced CTL response of HGP-30-coated EBV-transformed autologous B cell lines. This study was approved under an IND for the California Department of Health Services' Food and Drug Branch. They have provided excellent support and regulatory guidelines for this project. Future work will extend and confirm these initial observations.