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Mucosal infection and vaccination against feline immunodeficiency virus
C R Stokes1, S Finerty, T J Gruffydd-Jones
1Division of Molecular and Cellular Biology, University of Bristol, UK. chris.stokes@bris.ac.uk
Insights
Feline immunodeficiency virus (FIV) can infect cats through rectal and vaginal routes, impacting the gastrointestinal tract. Targeted lymph node vaccination shows promise in protecting cats from FIV infection.
Area of Science:
- Veterinary Virology
- Immunology
- Gastroenterology
Background:
- Feline immunodeficiency virus (FIV) infection in cats mirrors human immunodeficiency virus (HIV) progression to immunodeficiency.
- The gastrointestinal tract is a key site for HIV infection and pathology, with rectal and cervico-vaginal mucosae being common transmission routes.
- While biting is the primary FIV transmission route, rectal and vaginal infections are also possible in cats.
Purpose of the Study:
- To investigate FIV presence and host immune responses in the feline gastrointestinal tract following rectal infection.
- To evaluate various vaccination strategies for their efficacy in preventing FIV infection via rectal challenge.
- To explore the potential of targeted lymph node (TLN) vaccination in cats.
Main Methods:
- Detection of FIV core and envelope proteins, RNA, and proviral DNA in feline intestinal tissues using immunoperoxidase and molecular techniques.
- Analysis of immune cell populations (CD8+ cells) and cytokine mRNA levels (IL-2, IL-6, IL-10, gamma-IFN) in rectally infected cats.
- Assessment of different vaccination regimens (whole virus, V3, V3MAP, C2 with cholera toxin (CT), Quil A adjuvants) administered via various routes (rectal, intra-nasal, parenteral, TLN) followed by rectal challenge with FIV.
Main Results:
- FIV proteins and genetic material were detected in the colonic epithelium, lymphoid follicles, and lamina propria of infected cats.
- Asymptomatic cats with long-term rectal FIV infection showed increased CD8+ cells and elevated levels of specific cytokine mRNAs, suggesting a role for local immunity.
- Cholera toxin (CT) and Quil A adjuvants demonstrated route-dependent efficacy, with CT more effective for humoral and Quil A for cellular responses.
- Intra-nasal administration of CT was quantitatively more effective than rectal administration.
- Targeted lymph node (TLN) vaccination elicited stronger humoral and proliferative responses compared to rectal immunization.
- A preliminary study indicated the presence of FIV-specific cytotoxic T lymphocytes (CTLs) and protection from rectal challenge in all vaccinated cats.
Conclusions:
- The feline gastrointestinal tract is susceptible to FIV infection, with viral components found in intestinal tissues.
- Immune responses, including CD8+ cells and specific cytokines, may contribute to controlling FIV replication in asymptomatically infected cats.
- Vaccination strategies utilizing adjuvants like CT and Quil A, and delivery routes such as intra-nasal and TLN, show potential for inducing protective immunity against FIV.
- Targeted lymph node vaccination appears superior to rectal immunization for stimulating robust immune responses in cats.
- FIV-specific CTLs may play a role in protection against rectal FIV challenge.
Abstract:
Feline immunodeficiency virus (FIV) infection is a naturally occurring lentiviral infection of cats which progresses to immunodeficiency in a manner strikingly 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 infection and primary pathology. Although biting is the principle mode of transmission 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 lymphoid follice and occasional cells in the lamina propria. Further, in the intestine we have detected FIV RNA and proviral DNA in epithelial cells, colonic 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 these cats remained clinically healthy these results might suggest that both local antibody and class I restricted cytotoxic lymphocytes (CTLs) may play a role in control of viral replication. We have investigated a range of vaccination regimes for their ability to generate responses which would protect from rectal challenge with virulent virus. Cats have been immunized with 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 cholera toxin and Quil A are not influenced by the route of delivery (intraperitoneal (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 used as an adjuvant via the intra-nasal than the rectal route. Recently, we have begun to investigate if the promising results obtained with targeted lymph node (TLN) vaccination in monkeys could be reproduced in the cat. We have shown that TLN was more effective than rectal immunisation in stimulating both humoral and proliferative responses. In a preliminary study we have also been able to detect FIV specific CTLs and have observed protection from rectal challenge in four out of four cats.