Antibody-based protection against HIV infection by vectored immunoprophylaxis

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
A single injection of a viral vector that encodes antibodies able to neutralize most HIV strains protects humanized mice from HIV infection. The identification of broadly neutralizing antibodies against HIV has stimulated a search for vaccine immunogens that can elicit similar antibodies. This paper presents an alternative approach to boosting immunity against infectious diseases for which neutralizing antibodies are available. David Baltimore and colleagues have engineered adenovirus-associated vectors expressing a human antibody against HIV. A single injection of the vector induced lifelong expression of HIV-neutralizing antibodies that protect humanized mice from infection with a high dose of HIV. Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains1,2,3,4,5. These antibodies all exhibit an unusually high level of somatic mutation6, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen7. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes8,9,10, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.