Abstract
Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.
Highlights
Tens of millions of individuals are currently living with HIV-1
We will examine the obstacles presented by HIV-1 and the means by which a heterologous prime-boost vaccine might overcome them
In the early 1990s, the value of the heterologous prime boost in the context of HIV-1 vaccinations was demonstrated by Hu et al Briefly, investigators used a recombinant vaccinia virus that expressed an HIV-1 (BRU) envelope for the priming of small animals, and followed this with a purified HIV-1 envelope protein boost [108]
Summary
Tens of millions of individuals are currently living with HIV-1. In the United States alone, despite plentiful resources, there are an estimated one million individuals infected with HIV-1, and approximately 55,000 new infections each year [1,2]. The second vaccine component was a mixture of two CHOderived HIV-1 envelope proteins formulated in alum, named AIDSVAX B/E, produced by Vaxgen. These protein sequences derived from CRF01_AE A244 and MN [8]. When the outcome of vaccinations was evaluated by a modified intent-to-treat analysis, results showed that there were approximately 30% fewer infections in the vaccinated group compared to the placebo control group. These somewhat encouraging results provide a stepping stone for the production of improved vaccines. We will examine the obstacles presented by HIV-1 and the means by which a heterologous prime-boost vaccine might overcome them
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
