PROTECTIVE IMMUNITY INDUCED BY ROTAVIRUS DNA VACCINES

It is estimated that Group A rotavirus diarrhea causes as many as one million deaths per year in children worldwide, and effective vaccines will be essential for their control. Plasmid DNA vaccines encoding mur ine rotaviral proteins VP4, VP6, or VP7 were tested in adult BALB/c mi ce for their ability to induce immune responses and provide protection against rotavirus challenge. The vaccines were administered by inocul ation into cells of the epidermis with an Accell gene gun (Auragen, In c., Middleton, WI, USA). Each vaccine elicited rotavirus-specific seru m antibodies as measured by ELISA. Virus neutralizing antibodies were detected in mice receiving plasmid DNAs encoding for outer capsid prot eins VP4 and VP7, but not for VP6, an inner capsid protein, and all of the vaccines generated virus-specific CTL responses. Each vaccine was effective in protecting mice against infection after homotypic rotavi rus (100 ID50) challenge, showing reductions (P<0.0002) in viral excre tion measured over a 9 day period. Increased rotavirus-specific intest inal IgA antibodies were seen in vaccinated mice after rotavirus chall enge, particularly in mice that received the VP6 DNA vaccine. This sug gests that intracellular IgA-mediated neutralization may be involved i n protective immunity induced by the VP6 DNA vaccine, and may represen t a new mechanism for protection by DNA vaccines. (C) 1997 Elsevier Sc ience Ltd.