Mucosal infection and vaccination against feline immunodeficiency virus

Feline immunodeficiency virus (FIV) infection is a naturally occurring lent iviral infection of cats which progresses to immunodeficiency in a manner s trikingly similar to that observed in HIV infection in man. The rectal and cervico-vaginal mucosae are common routes of transmission of HIV and it has been shown that the gastrointestinal tract is an important site of HIV inf ection and primary pathology. Although biting is the principle mode of tran smission for FIV, we have shown that it is possible to reliably infect cats via both the rectal and vaginal routes. Using a biotin-streptavidin linked immunoperoxidase technique we have detected FIV core and envelope proteins in the colonic follicle associated epithelial cells, cells within the lymp hoid follice and occasional cells in the lamina propria. Further. in the in testine we have detected FIV RNA and proviral DNA in epithelial cells, colo nic lymphoid aggregates and isolated lamina propria cells. We have studied a group of asymptotic cats which have been rectally infected with FIV for 1 year or longer and shown an increase in the number of lamina propria CD8() cells and greater levels of IL-2, IL-6, IL-10 and gamma-IFN mRNA. Since t hese cats remained clinically healthy these results might suggest that both local antibody and class I restricted cytotoxic lymphocytes (CTLs) may pla y a role in control of viral replication. We have investigated a range of v accination regimes for their ability to generate responses which would prot ect from rectal challenge with virulent virus. Cats have been immunized wit h whole virus (FIV-pet, FIV-GLA-8), V3, V3MAP or C2 with cholera toxin (CT) , or Quil A based adjuvants via rectal, intra-nasal, parenteral or targeted lymph node routes, and challenged rectally with ten mucosal cat infectious doses (MCID) of FIV-GLA-8. We have shown that the adjuvant effects of chol era toxin and Quil A are not influenced by the route of delivery (intraperi toneal (i.p.) versus rectal) with CT more effective in stimulating humoral and Quil A more effective in stimulating cellular responses to FIV antigens . However we have shown that, quantitatively, CT is more effective when use d as an adjuvant via the intra-nasal than the rectal route. Recently, we ha ve begun to investigate if the promising results obtained with targeted lym ph node (TLN) vaccination in monkeys could be reproduced in the cat. We hav e shown that TLN was more effective than rectal immunisation in stimulating both humoral and proliferative responses. In a preliminary study we have a lso been able to detect FIV specific CTLs and have observed protection from rectal challenge in four out of four cats. (C) 1999 Elsevier Science B.V. All rights reserved.