Nonreplicating vectors in HIV vaccines

Abstract

Purpose of review We review the broad spectrum of nonreplicating viral vectors which have been studied extensively, from preclinical studies through clinical efficacy trials, and include some of our most promising HIV vaccine candidates. Recent findings The success of the RV144 trial, with an ALVAC (canarypox)-based regimen, contrasts with the failures of the Adenovirus 5-based regimens in the Step study, the Phambili study (HVTN 503), and the HVTN 505 study which was recently modified to halt vaccinations due to clinical futility. Summary The safety profile, immunogenicity, and variety of available candidates make the nonreplicating viral vectors attractive in HIV vaccine development. Building from the success of the RV144 study, further studies of Orthopoxvirus-based vaccines, including Vaccinia-based vaccines, are ongoing and planned for the future. Despite the failures of the Ad5-based vaccines in clinical efficacy trials, other adenovirus serotypes remain promising candidates, especially in prime-boost combination with other products, and with the potential use of mosaic inserts. Other nonreplicating viral vectors such as the rhabdoviruses, alphaviruses and the non-human adenoviruses, provide additional avenues for exploration.

A Bivalent, Chimeric Rabies Virus Expressing Simian Immunodeficiency Virus Envelope Induces Multifunctional Antibody Responses

“…98 In addition, efficacy using Ad5-based vectors was limited in phase IIb clinical trials. 96 Early human clinical studies using a canarypox-based vector (ALVAC) demonstrated modest HIV antibodies and low cellular responses. 99,100 However, a prime-boost regimen with ALVAC and a recombinant gp120 boost showed significant protection against acquiring HIV infection in the RV144 vaccine trial.…”

“…26 Other viral vector systems have been tested for their ability to induce HIV-specific B cell responses. [95][96][97] Replicationdeficient poxvirus-and adenovirus-based vaccines are perhaps the best studied viral vectors in the context of an HIV vaccine. Early immunogenicity studies of nonreplicating adenovirus expressing HIV-1 env in mice showed that a boost was required to induce anti-HIV-1 Env antibodies using higher titers of vaccine.…”

Vaccine Nanoparticles for Protection Against HIV Infection

“…These live-vector-based vaccines use genetically attenuated pathogens to express viral antigens and stimulate the host immune system. Although live-vector-based vaccines can induce robust T-cell and B-cell immune responses, manufacturing of live organism-based vaccines as well as inherent antivector immunity observed in the general population are major obstacles to overcome [16][17][18]. A prime example of the latter is Merck and Co.'s (NJ, USA) STEP study, Phase II clinical trial that was stopped in 2007 [19].…”

Interleukin-1- and Type I Interferon-Dependent Enhanced Immunogenicity of an NYVAC-HIV-1 Env-Gag-Pol-Nef Vaccine Vector with Dual Deletions of Type I and Type II Interferon-Binding Proteins

“…Poxviruses have been studied extensively as gene transfer vectors (10). A large packaging capacity for recombinant DNA, precise virusspecific control of target gene expression, a lack of persistence of genomic integration in the host, and high immunogenicity when used as a vaccine make poxviruses very attractive as gene delivery systems for the development of new vaccines (11).…”