Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the modified vaccinia Ankara (MVA) virus, and a replication incompetent adenovirus type 5 (Ad5) vector-expressing the SIV gag protein for their ability to elicit such immune responses in monkeys. The vaccines were tested either as a single modality or in combined modality regimens. Here we show that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. After challenge with a pathogenic HIV-SIV hybrid virus (SHIV), the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the virus infection. The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine.

We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.

Helicobacter pylori has been directly linked with active chronic gastritis, peptic ulceration, and gastric adenocarcinoma in humans. Although a substantial portion of the human population is colonized with H. pylori, the patterns of transmission of the organism remain in doubt, and reservoir hosts have not been identified. This study documents the isolation of H. pylori from domestic cats obtained from a commercial vendor. The isolation of H. pyloni from these cats was confirmed by morphologic and biochemical evaluations, fatty acid analysis, and 16S rRNA sequence analysis. H. pyloni was cultured from 6 cats and organisms compatible in appearance with H. pylori were observed in 15 additional cats by histologic examination. In most animals, H. pylori was present in close proximity to mucosal epithelial cells or in mucus layers of the glandular or surface epithelium. Microscopically, H. pyloni-infected cat stomachs contained a mild to severe diffuse lymphoplasmacytic infiltrate with small numbers of neutrophils and eosinophils in the subglandular and gastric mucosae. Lymphoid follicles were also noted, particularly in the antrum, and often displaced glandular mucosal tissue. Thus, the domestic cat may be a potential model for H. pyloni disease in humans. Also, the isolation of H. pyloni from domestic cats raises the possibility that the organism may be a zoonotic pathogen, with transmission occurring from cats to humans.

It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys using plasmidencoded HIV-1 env DNA as the immunogen. In the present study, we show that the addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species. Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immmunodeficiency virus mac backbone (SHIV-HXBc2). The potent immunity and protection seen in these pilot experiments suggest that a DNA prime͞DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection.