RESUMEN
Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains.
Asunto(s)
Adyuvantes Inmunológicos , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/inmunología , Orthomyxoviridae/inmunología , Escualeno/inmunología , Animales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Especificidad de Anticuerpos , Fosfatos de Calcio/inmunología , Línea Celular , Emulsiones , Femenino , Inmunoglobulina G/sangre , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/administración & dosificación , Inyecciones Intramusculares , Interferón gamma/biosíntesis , Ácido Láctico/inmunología , Ratones , Ratones Endogámicos BALB C , Pruebas de Neutralización , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Polisorbatos , Bazo/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunologíaRESUMEN
Although alum is the most commonly used vaccine adjuvant, it has some limitations for use with the next generation recombinant antigens. We explored the use of alternative adjuvant formulations (poly lactide co-glycolide (PLG) microparticles, MF59 emulsion, CAP and l-tyrosine suspension) in comparison with five different vaccine antigens--namely, diphtheria toxoid (DT), tetanus toxoid (TT), HBsAg, Men C conjugate and MB1. The results indicated that although alum was optimal for bacterial toxoid based vaccines, it was not highly potent for MB1, Men C or HBsAg antigens. MF59 emulsion stood out as a good alternative to alum for TT, HBsAg, MB1 and Men C vaccines. On the other hand l-tyrosine suspension and CAP did not enhance immune responses over alum with most antigens. PLG microparticles were comparable or better than alum with both MB1 and Men C conjugate vaccine. The study indicates that it is possible to replace alum with other adjuvant formulations like MF59 and PLG and maintain and/or improve immune responses with some vaccine antigens.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Vacunas/inmunología , Compuestos de Alumbre/farmacología , Animales , Fosfatos de Calcio/farmacología , Toxoide Diftérico/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Inmunización , Ácido Láctico/farmacología , Vacunas Meningococicas/inmunología , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , Ácido Poliglicólico/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/farmacología , Polisorbatos/farmacología , Escualeno/farmacología , Toxoide Tetánico/inmunologíaRESUMEN
A novel cationic emulsion was developed to adsorb plasmid DNA and improve intracellular delivery of plasmid DNA upon immunization. The emulsion developed, had a highly uniform particle and charge distribution. Based on observations with cationic microparticles, the cationic emulsion was evaluated in vivo in mice and rabbits with a model HIV-1 pCMVp55 gag DNA. In both these species, the cationic emulsion engendered higher antibody responses than those obtained with naked DNA. The cationic emulsion also maintained the cellular responses seen with naked DNA at the same doses.