RESUMEN
Stearly tyrosine has been described in the literature as a candidate adjuvant for human vaccines. More recently, other stearyl esters have been reported to be adjuvant-active. This preliminary study assesses the adjuvanticity of stearyl amides, including the amide analogue of stearyl tyrosine: tyrosyl stearylamine. This study indicates that phenylalanylethanolamine O-stearate induces a significant antibody response and a favourable isotype distribution.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Fenilalanina/análogos & derivados , Estearatos/farmacología , Tirosina/análogos & derivados , Animales , Formación de Anticuerpos/efectos de los fármacos , Femenino , Ratones , Ratones Endogámicos BALB C , Fenilalanina/farmacología , Tirosina/farmacologíaRESUMEN
A new family of immunoadjuvants, long-chain stearyl esters of amino acids and peptides, are described and examined with bacterial and viral vaccines. The parent compound, stearyl tyrosine, displayed significant adjuvant activity with these vaccines. Stearyl glycyl glycine displayed superior activity with viral vaccines. A number of analogues of stearyl tyrosine were adjuvant-active. Further, these adjuvants were able to elicit a neutralizing antibody response. Stearyl tyrosine and stearyl ester analogues represent promising adjuvants for human vaccines.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Tirosina/análogos & derivados , Secuencia de Aminoácidos , Aminoácidos/farmacología , Animales , Formación de Anticuerpos/efectos de los fármacos , Especificidad de Anticuerpos , Ésteres/inmunología , Ésteres/farmacología , Femenino , VIH/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/farmacología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Neisseria meningitidis/inmunología , Oligopéptidos/farmacología , Poliovirus/inmunología , Toxoides/inmunología , Toxoides/farmacología , Tirosina/inmunología , Tirosina/farmacología , Proteínas Virales/inmunología , Proteínas Virales/farmacologíaRESUMEN
We describe the enhancement of the antibody response against hepatitis B surface Ag by octadecyl L-tyrosine, a synthetic adjuvant designed to exert its adjuvant effect in a manner similar to that of alum because it binds soluble Ag and releases it slowly from the site of injection. Our data demonstrate that octadecyl L-tyrosine showed a significant enhancement of the antihepatitis B surface Ag response compared to that of alum in the secondary response. The most striking difference between octadecyl L-tyrosine and alum in the antihepatitis B surface Ag antibody response was the absence of IgE-specific antibodies subsequent to immunization of the Ag in octadecyl L-tyrosine. Both the optical isomers of the octadecyl esters of tyrosine were adjuvant active, however, the racemic mixture showed a significantly lowe adjuvant activity. This adjuvant has great potential to be used in humans because it is devoid of side effects as assessed by the lack of acute and chronic toxicity in mice and rats, pyrogenicity in rabbits, formation of granuloma in cats, and adjuvant arthritis in rats.