Serum and intestinal isotype antibody responses and correlates of protective immunity to human rotavirus in a gnotobiotic pig model of disease.

Abstract

We examined the antibody responses and protection to a human rotavirus (HRV) in gnotobiotic (Gn) pigs. Pigs were perorally (p.o.) inoculated with attenuated (group 1), virulent (group 2), or inactivated (group 3) Wa (P1A[8]G1) HRV. A fourth group was inoculated intramuscularly (i.m.) with inactivated Wa HRV in adjuvant. After p.o. challenge with virulent Wa HRV at post-inoculation day 21, most group 1, 3 and 4 pigs shed virus and developed diarrhoea, whereas this occurred in only a few group 2 pigs. Antibodies to HRV (IgM, IgA or IgG) were detected in serum and intestinal contents of pigs of all groups after virus inoculation or challenge, and the antibody titres in intestinal contents, although lower, showed similar kinetics to the serum responses. There was no correlation between protection and neutralizing antibody titres of serum or intestinal contents, but a positive correlation existed between protection and serum IgA, intestinal IgA and intestinal IgG antibody titres. These findings suggest that serum IgA antibodies to HRV could act as an indicator of IgA antibodies in the intestine after rotavirus infection. The virulent HRV elicited protective immunity and higher levels of serum and intestinal IgA antibodies to HRV compared to attenuated and inactivated HRV. These findings suggest that more efficient mucosal delivery systems and/or adjuvants are needed to enhance the intestinal immune responses to attenuated or inactivated HRV if more successful vaccination is to be achieved in neonates.