Abstract
The field of HIV prevention has indeed progressed in leaps and bounds, but with major limitations of the current prevention and treatment options, the world remains desperate for an HIV vaccine. Sadly, this continues to be elusive, because more than 30 years since its discovery there is no licensed HIV vaccine. Research aiming to define immunological biomarkers to accurately predict vaccine efficacy have focused mainly on systemic immune responses, and as such, studies defining correlates of protection in the genitorectal mucosa, the primary target site for HIV entry and seeding are sparse. Clearly, difficulties in sampling and analysis of mucosal specimens, as well as their limited size have been a major deterrent in characterizing the type (mucosal antibodies, cytokines, chemokines, or CTL), threshold (magnitude, depth, and breadth) and viral inhibitory capacity of HIV-1-specific immune responses in the genitorectal mucosa, where they are needed to immediately block HIV acquisition and arrest subsequent virus dissemination. Nevertheless, a few studies document the existence of HIV-specific immune responses in the genitorectal mucosa of HIV-infected aviremic and viremic controllers, as well as in highly exposed persistently seronegative (HEPS) individuals with natural resistance to HIV-1. Some of these responses strongly correlate with protection from HIV acquisition and/or disease progression, thus providing significant clues of the ideal components of an efficacious HIV vaccine. In this study, we provide an overview of the key features of protective immune responses found in HEPS, elite and viremic controllers, and discuss how these can be achieved through mucosal immunization. Inevitably, HIV vaccine development research will have to consider strategies that elicit potent antibody and cellular immune responses within the genitorectal mucosa or induction of systemic immune cells with an inherent potential to home and persist at mucosal sites of HIV entry.
Highlights
The past three decades have witnessed the transformation of HIV/AIDS from a fatality to a chronic manageable disease but the situation remains far from ideal as the epidemic continues to spread
According to the UNAIDS report 2013, an estimated 35 million people are living with HIV, 2.3 million new infections, and 1.6 million AIDS-related deaths were documented at the end of 2012
Owing to the enormous hurdles relating to mucosal sampling methodologies and limited sample volumes, immune correlates of protection against HIV-1 in the genital mucosa have not been routinely tested during clinical trials that evaluate immunogenicity and vaccine efficacy [165]
Summary
The past three decades have witnessed the transformation of HIV/AIDS from a fatality to a chronic manageable disease but the situation remains far from ideal as the epidemic continues to spread. HAART has increased the lifespan of infected people [2], but has had other significant health benefits including reduced risk of opportunistic infections such as tuberculosis and AIDS-defining cancers, namely Kaposi sarcoma and cervical cancer [1, 3]. The recent introduction of universal testing and treatment (UTT) followed by immediate initiation of ART to all those testing HIV positive irrespective of clinical stage or CD4 count [16,17,18,19] will have a huge impact on the epidemic, the reality is that wider scale implementation will inevitably be logistically and financially overwhelming [20]. Microbicides [8] and male www.frontiersin.org
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