1887

Abstract

An effective vaccine against infection with human immunodeficiency virus type 1 (HIV-1) is thought likely to require both a humoral and a CTL immune response. A non-replicating adenovirus vector system has been developed that can induce both a humoral and CTL response to HIV-1 envelope in mice. It is demonstrated that the stimulatory / 5′ splice-donor site sequence is required for efficient expression of HIV-1 by this adenovirus vector system. can be provided bicistronically or to result in good expression of . A humoral immune response was detected after two immunizations with a bicistronic recombinant adenovirus (RAd142). The response was dose dependent, 5×10 p.f.u. inducing a response in some, but not all, animals and 1×10 p.f.u. giving a consistent antibody response. However, CTLs were induced by the lower dose of virus and after only one immunization with the higher dose. A positive CTL response was also seen consistently when the two monocistronic adenoviruses (RAd501 expressing and RAd46 expressing ) were given together, although two immunizations were required to give approximately the same level of response as seen with the bicistronic virus. RAd501 on its own also gave a low CTL response when two immunizations were given. It is suggested that a lower level of expression is required to produce a CTL response than a humoral response and that this non- replicating adenovirus vector is a good system for inducing CTL.

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1999-10-01
2020-01-21
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