Antibody-Secreting Cell Responses and Protective Immunity Assessed in Gnotobiotic Pigs Inoculated Orally or Intramuscularly with Inactivated Human Rotavirus

Abstract

Newborn gnotobiotic pigs were inoculated twice perorally (p.o.) (group 1) or intramuscularly (i.m.) (group 2) or three times i.m. (group 3) with inactivated Wa strain human rotavirus and challenged with virulent Wa human rotavirus 20 to 24 days later. To assess correlates of protection, antibody-secreting cells (ASC) were enumerated in intestinal and systemic lymphoid tissues from pigs in each group at selected postinoculation days (PID) or postchallenge days. Few virus-specific ASC were detected in any tissues of group 1 pigs prior to challenge. By comparison, groups 2 and 3 had significantly greater numbers of virus-specific immunoglobulin M (IgM) ASC in intestinal and splenic tissues at PID 8 and significantly greater numbers of virus-specific IgG ASC and IgG memory B cells in spleen and blood at challenge. However, as for group 1, few virus-specific IgA ASC or IgA memory B cells were detected in any tissues of group 2 and 3 pigs. Neither p.o. nor i.m. inoculation conferred significant protection against virulent Wa rotavirus challenge (0 to 6% protection rate), and all groups showed significant anamnestic virus-specific IgG and IgA ASC responses. Hence, high numbers of IgG ASC or memory IgG ASC in the systemic lymphoid tissues at the time of challenge did not correlate with protection. Further, our findings suggest that inactivated Wa human rotavirus administered either p.o. or parenterally is significantly less effective in inducing intestinal IgA ASC responses and conferring protective immunity than live Wa human rotavirus inoculated orally, as reported earlier (L. Yuan, L. A. Ward, B. I. Rosen, T. L. To, and L. J. Saif, J. Virol. 70:3075–3083, 1996). Thus, more efficient mucosal delivery systems and rotavirus vaccination strategies are needed to induce intestinal IgA ASC responses, identified previously as a correlate of protective immunity to rotavirus.

Isotype-specific antibody-secreting cells in systemic and mucosal associated lymphoid tissues and antibody responses in serum of conventional pigs inoculated with PEDV

“…As a constant in our results, the number of IgG ASC in gut associated tissues was higher than the number of IgA ASC. This fact has also been described in previous reports (Van Cott et al, 1993;Yuan et al, 1996Yuan et al, , 1998 studying immunity by ELISPOT in TGEV and rotavirus infections. Even though there is no clear explanation for this fact, the possibility of extraintestinal stimulation of the immune system has been proposed.…”

Induction of mucosal immune responses and protection against enteric viruses: rotavirus infection of gnotobiotic pigs as a model

“…A lack of understanding of mechanisms to induce intestinal immunity and the correlates of protective immunity in neonates has impaired development of safe and effective vaccines against enteric viruses for farm animals and children. Protection induced by candidate vaccines observed in studies using lab animals, such as mouse and rabbit models of rotavirus subclinical infections often do not predict the protective ef®cacy of these vaccines against clinical infections in studies of neonatal large animals O'Neal et al, 1998;McNeal et al, 1999a,b;Yuan et al, 1998Yuan et al, , 2000Welter and Welter, 1990). Efforts to identify immunologic correlates of protective immunity to rotavirus infection using knockout mice for selected immune-related genes, passive lymphocyte transfer experiments, and immunodepletion of selected populations of lymphocytes by the injection of speci®c monoclonal antibodies have shown that none of the known effectors for acquired immune responses (CD4 or CD8 T-cells, antibodies, interferon-g, perforin, etc.)…”

In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus

“…Yet, despite the numerous trials and decades of research, effective vaccines are still not available for these or other viral agents that cause gastroenteritis. Although, research efforts have appeared promising, vaccine field trials continue to produce inadequate results or fail entirely (de Leeuw et al, 1980;Myers and Snodgrass, 1982;Snodgrass et al, 1982;Waltner-Toews et al, 1985;Yuan et al, 1998). The inadequacy of rotavirus vaccines may be explained, in part, by the complex antigenic diversity of the group A rotaviruses (Woode et al, , 1987Zheng et al, 1989;Hardy et al, 1991;Parwani et al, 1993;, and by doubts concerning which of the two main antigens, VP4 or VP7, is the most important antigen to induce immune protection (Ward et al, 1993;.…”