Front. Immunol., 07 May 2014 | doi: 10.3389/fimmu.2014.00202

Induction of potent and long-lived antibody and cellular immune responses in the genitorectal mucosa could be the critical determinant of HIV vaccine efficacy

  • 1Institute of Tropical and Infectious Diseases, College of Health Sciences, University of Nairobi, Nairobi, Kenya
  • 2The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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.

Keywords: HIV-1, HIV vaccines, elite controllers, long-term non-progressors, highly exposed persistently seronegative, mucosal immunity

Citation: Chanzu N and Ondondo B (2014) Induction of potent and long-lived antibody and cellular immune responses in the genitorectal mucosa could be the critical determinant of HIV vaccine efficacy. Front. Immunol. 5:202. doi: 10.3389/fimmu.2014.00202

Received: 10 March 2014; Accepted: 23 April 2014;
Published online: 08 May 2014.

Edited by:

Magdalena Plebanski, Monash University, Australia

Reviewed by:

Mirko Trilling, University Duisburg-Essen, Germany; Essen University Hospital, Germany
Emilio Luis Malchiodi, University of Buenos Aires, Argentina
John Stambas, Deakin University, Australia

Copyright: © 2014 Chanzu and Ondondo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Beatrice Ondondo, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK e-mail:

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