SYSTEMIC AND INTESTINAL ANTIBODY-SECRETING CELL RESPONSES AND CORRELATES OF PROTECTIVE IMMUNITY TO HUMAN ROTAVIRUS IN A GNOTOBIOTIC PIG MODEL OF DISEASE

Neonatal gnotobiotic pigs orally inoculated with virulent (intestinal- suspension) Wa strain human rotavirus (which mimics human natural infe ction) developed diarrhea, and most pigs which recovered (87% protecti on rate) were immune to disease upon homologous virulent virus challen ge at postinoculation day (PID) 21. Pigs inoculated with cell culture- attenuated Wa rotavirus (which mimics live oral vaccines) developed su bclinical infections and seroconverted but were only partially protect ed against challenge (33% protection rate). Isotype-specific antibody- secreting cells (ASC) were enumerated at selected PID in intestinal (d uodenal and ileal lamina propria and mesenteric lymph node [MLN]) and systemic (spleen and blood) lymphoid tissues by using enzyme-linked im munospot assays. At challenge (PLD 21), the numbers of virus-specific immunoglobulin A (IgA) ASC, but not IgG ASC, in intestines and blood w ere significantly greater in virulent-Wa rotavirus-inoculated pigs tha n in attenuated-Wa rotavirus-inoculated pigs and were correlated (corr elation coefficients: for duodenum and ileum, 0.9; for MLN, 0.8; for b lood, 0.6) with the degree of protection induced. After challenge, the numbers of IgA and IgG virus-specific ASC and serum-neutralizing anti bodies increased significantly in the attenuated-Wa rotavirus-inoculat ed pigs but not in the virulent-Wa rotavirus-inoculated pigs (except i n the spleen and except for IgA ASC in the duodenum). The transient ap pearance of IgA ASC in the blood mirrored the IgA ASC responses in the gut, albeit at a lower level, suggesting that IgA ASC in the blood of humans could serve as an indicator for IgA ASC responses in the intes tine after rotavirus infection. To our knowledge, this is the first re port to study and identify intestinal IgA ASC as a correlate of protec tive active immunity in an animal model of human-rotavirus-induced dis ease.