HIV-1 Vaccine Strategies Utilizing Viral Vectors Including Antigen- Displayed Inoviral Vectors

Abstract

Antigen-presenting viral vectors have been extensively used as vehicles for the presentation of antigens to the immune system in numerous vaccine strategies. Particularly in HIV vaccine development efforts, two main viral vectors have been used as antigen carriers: (a) live attenuated vectors and (b) virus-like particles (VLPs); the former, although highly effective in animal studies, cannot be clinically tested in humans due to safety concerns and the latter have failed to induce broadly neutralizing anti-HIV antibodies. For more than two decades, Inoviruses (non-lytic bacterial phages) have also been utilized as antigen carriers in several vaccine studies. Inoviral vectors are important antigen-carriers in vaccine development due to their ability to present an antigen on their outer architecture in many copies and to their natural high immunogenicity. Numerous fundamental studies have been conducted, which have established the unique properties of antigen-displayed inoviral vectors in HIV vaccine efforts. The recent isolation of new, potent anti-HIV broadly neutralizing monoclonal antibodies provides a new momentum in this emerging technology.

Architectural Insight into Inovirus-Associated Vectors (IAVs) and Development of IAV-Based Vaccines Inducing Humoral and Cellular Responses: Implications in HIV-1 Vaccines

“…The inovirus display technology has also been applied in vaccination strategies against HIV-1 [ 130 ]. However, unlike the successful development of vaccines against non-HIV-1 parasites, these efforts failed.…”

The development of inovirus-associated vector vaccines using phage-display technologies

“…Despite the efficacy of these inovirus-based vaccines against a variety of infectious and non-infectious diseases, there are still many diseases for which effective vaccines have not been developed using phage display or other methods. For example as discussed above, despite extensive work with inoviruses beginning in 1993 by Keller et al [66], there has been very little success developing a (HIV-1) vaccine [95]. While four major epitopes on the HIV-1 envelope gp41 and gp120 glycoproteins have been identified [96][97][98], inducing the production of effective antibodies has not been successful [70].…”