Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies
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AIDS Research and Therapy Open Access
REVIEW
Development of an anti‑HIV vaccine eliciting broadly neutralizing antibodies Yousuf Ahmed, Meijuan Tian and Yong Gao*
Abstract The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response. Keywords: HIV-1, Diversity, Broadly neutralizing antibody, Polyvalent vaccine, B cell maturation
Background According to the WHO, there were ~36.7 million people worldwide living with HIV/AIDS by the end of 2015 and 2.1 million new HIV infections in 2015. In Canada, there were estimated 75,500 people living with HIV infection or AIDS at the end of 2014, a 9.7% increase from 2011, with more than 2500 people are newly infected each year. Unfortunately, even after over 30 years of intensive research, there is still no effective anti-HIV vaccine. This mini review will focus on the development of anti-HIV vaccine targeting elicitation of broadly neutralizing antibodies (bNAbs) against extremely diverse HIV strains. HIV diversity and vaccine development The extreme genetic diversity of HIV, as a result of high baseline rates of viral mutation and replication, has been a great challenge for HIV vaccine development [1, 2]. There are two types of HIV: HIV-1, predominant throughout the world, and HIV-2, found primarily in West/Central Africa. HIV-1 contains four groups: M (main), O (outlier), N (non-M/non-O), and P (pending).
*Correspondence: [email protected] Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
Group M is further subdivided into 9 distinct subtypes [3] and numerous additional circulating recombinant forms (CRF) [4]. Viruses within the same subtype differ by up to 20%, within the highly variable env region by up to 38%. Furthermore, the virus continuously diversifies in infected individuals, resulting in the virus quasispecies varying up to 5% genetic difference in the same patient at different time points. These quasispecies compose of a unique and highly complex mixture of variants in infected individuals, and ultimately give rise to a highly diverse global virus population.
Development of broadly effective anti‑HIV vaccine It is widely thought that an effective strategy to prevent HIV infection will likely come from T cell and B-cell mediated immunity, especially a broadly neutralizing an
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