Current HIV Research - Volume 5, Issue 6, 2007

Each year, more than 5 million individuals are newly infected with HIV-1 [1]. To address this, the development of an HIV/AIDS vaccine has remained one of the highest priorities in biomedical research for the last 25 years. During this time, we have witnessed some success with the development of antiretroviral therapies capable of lowering the viral loads and decreasing the severity of disease. While treatment has extended the t Read More

So far, all efforts to engineer immunogens that would elicit broadly reactive anti-HIV neutralizing antibody responses have not been successful. In the past few years, however, key information on the structure of the epitopes recognized by several broadly reactive anti-HIV neutralizing antibodies (NAbs), the structures of these NAbs themselves and the molecular interaction between these NAbs and their epitopes has e Read More

To date HIV-1 vaccines have not been able to elicit potent, long lasting, and broadly neutralizing antibodies to the virus. Our knowledge of HIV envelope glycoprotein (Env) structure/function and the existence of a handful of broadly neutralizing antibodies is guiding rational immunogen design. We review here the potential targets on the HIV Env (the glycan shield, the CD4 binding site, the coreceptor binding site, Env fusi Read More

A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely produced by infected subjects, nor are they induced by various immunogens designed to exp Read More

The enormous diversity of the human immunodeficiency virus (HIV) has led to the idea that designing vaccines to specific geographic regions, or clades, could simplify the complexity of the task. Yet, despite the sequence diversity, all HIV viruses known to date interact with the same cellular receptors (CD4 and/or a coreceptor, CCR5 or CXCR4). In this review we examine the existing evidence to support a clade-specific vaccin Read More

The HIV surface glycoprotein, gp120, contains conserved and functional domains that exist within a viral envelope spike that is otherwise highly variable with respect to conformation, sequence and structure. Termed CD4-induced epitopes, these domains are stabilized on transition state gp120 structures as a consequence of CD4 receptor engagement. These nuggets of conservation naturally attract the attention of those Read More

Centralized HIV-1 genes (consensus, most recent common ancestor and center of the tree) have recently been explored for induction of broadly reactive immune responses to overcome the extraordinary genetic diversity among HIV- 1 strains. Although all of these strategies are based on artificial sequences predicted by computer programs, they retain biological function, and use the CCR5 co-receptor for entry into target Read More

In most cases of HIV-1 transmission, only a subset of variants is transmitted from the index case to the newly infected individual. Understanding the characteristics of these transmitted variants may aid in developing new methods to halt the spread of HIV-1. Studies evaluating the genotypic and antigenic properties of transmitted variants have provided insights into how the selective pressures applied during different modes of tr Read More

The mucosal immune response to HIV weighs in heavily on the battle against it, as the majority of infections occur via the mucosal route. The antibody response in the mucosae, specifically the genital tract, is characterized by binding and, in some studies, neutralizing HIV-specific IgG and IgA antibodies. Ample evidence, however, points to discrepancies and difficulties in the detection of HIV-specific IgA in HIV-positive subje Read More

Over the last two decades, use of SIV for experimental infection of Asian macaques has provided important leads in the quest for an AIDS vaccine, served as the genesis of recombinant SIV/HIV viruses (SHIV), and perhaps most importantly, helped establish or confirm biological relevance for a variety of hypotheses related to the host immune response to infection and the corresponding viral strategies for evading that response Read More

Antibody (Ab) mediated neutralization is a crucial means of host resistance to many pathogens and will most likely be required in the development of a vaccine to protect against HIV-1. Here we examine mechanistic aspects of HIV-1 neutralization with attention to recent studies on the stoichiometric, kinetic and thermodynamic parameters involved. Neutralization of HIV-1, as with any microbe, minimally requires an initi Read More

Upon viral exposure, antibodies serve as a first line of defense and can act by preventing infection or reducing the viral burden. The ability of antibodies to confer protection against HIV has been demonstrated by several studies using the passive transfer of neutralizing antibodies in the non-human primate challenge model. Therefore, efforts have been made to induce a similarly protective humoral immune response by Read More

The HIV-1/AIDS epidemic continues to escalate, and a protective vaccine remains elusive. The first vaccine candidate, gp120, did not induce broadly neutralizing antibodies (nAbs) against primary HIV-1 isolates and was ineffective in phase III clinical trials. Attention then focused on generating cytotoxic lymphocyte (CTL)-based vaccines. Interest in anti-HIV-1 nAbs was renewed when passive immunization with human Read More