RESUMEN
OBJECTIVE: Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A) substantially reduces the antigen dose required to produce a putatively protective humoral response and promotes cross-clade neutralizing responses. We determined the effect of adjuvantation on antibody persistence and B- and T-cell-mediated immune responses. METHODS: Two vaccinations with a split-virion A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 µg hemagglutinin and formulated with or without adjuvant were administered to groups of 50 volunteers aged 18-60 years. RESULTS: Adjuvantation of the vaccine led to better persistence of neutralizing and hemagglutination-inhibiting antibodies and higher frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional H5N1-specific CD4 T cells were detected at baseline and were amplified by vaccination. Expansion of CD4 T cells was enhanced by adjuvantation. CONCLUSION: Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and induces stronger T- and B-cell responses. The cross-clade T-cell immunity indicates that the adjuvanted vaccine primes individuals to respond to either infection and/or subsequent vaccination with strains drifted from the primary vaccine strain.
Asunto(s)
Adyuvantes Inmunológicos , Brotes de Enfermedades/prevención & control , Inmunidad Celular , Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza/administración & dosificación , Gripe Humana , Vacunación , Vacunas de Productos Inactivados/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Adolescente , Adulto , Secuencia de Aminoácidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Reacciones Cruzadas/inmunología , Femenino , Hemaglutininas/sangre , Hemaglutininas/inmunología , Humanos , Inmunidad Humoral , Memoria Inmunológica , Subtipo H5N1 del Virus de la Influenza A/química , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/sangre , Vacunas contra la Influenza/química , Vacunas contra la Influenza/inmunología , Gripe Humana/sangre , Gripe Humana/inmunología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Vacunas de Productos Inactivados/sangre , Vacunas de Productos Inactivados/química , Vacunas de Productos Inactivados/inmunologíaRESUMEN
The major envelope protein of the hepatitis B virus (HBV), the HBsAg, constitutes the current preventative vaccine, which represents the first subunit viral vaccine developed. The genetics of the immune response to HBsAg has been extensively studied both in humans and mice. Murine studies begun over 20 years ago indicated that at least two MHC class II and one MHC class III genes regulate anti-HBs immune responses. Additional MHC-linked genes influence the immune responses to the higher molecular weight (pre-S) components of the HBV envelope. The murine studies predicted even more complex MHC gene regulation of human immune responses to the HBsAg and that complexity certainly has been demonstrated during the ensuing years. This brief review is an attempt to summarize our current understanding of the MHC genes that influence the immune response to the HBsAg and possible mechanisms of action.