Current Drug Targets - Infectious Disorders - Volume 5, Issue 2, 2005

The devastation caused by HIV and AIDS has touched virtually every world region. One concern is that the unrelenting nature of the HIV pandemic fosters a disposition, not of fear and determination, but of tolerance and complacency.

This survey covers the immunological background to development of an HIV vaccine, starting from an overview of present understanding of the mechanisms of immunoregulation. It follows the uptake, processing and presentation of an antigen, from its initial uptake by a dendritic cell and its deposit on the dendrites of follicular dendritic cells. It pursues the antigen through uptake by B cells, presentation of epitopes to helper T Read More

More than 20 million people have died since the discovery of human immunodeficiency virus (HIV), yet a broadly reactive AIDS vaccine remains elusive. Neutralizing antibody (nAb) response-based vaccine strategies were the first to be tested; however, when the difficulty in neutralizing primary HIV isolates was recognized, vaccine development focused instead on generating cytotoxic T-lymphocyte (CTL) responses. Rece Read More

The prevention of HIV-1 by vaccination has proven to be a formidable task. In an ongoing endeavor to end the HIV-1 pandemic, scientists seek vaccines that will elicit quantitatively and qualitatively robust B-cell and T-cell activities. Given that cytotoxic T-lymphocytes (CTL) play a substantial role in the immunological control of immunodeficiency virus infections, this review will focus on vaccines designed to elicit HIV-1-specific Read More

Successful HIV vaccine strategies will likely require the induction of robust cellular immune responses, in addition to strong humoral responses. Unfortunately, there is no clear molecular definition of an effective HIV-specific CD8 T cell response. In this review, we discuss the differentiation of CD8 T cells in response to acute and chronic viral infections. We then apply concepts derived from these studies to predict the desirable Read More

Inactivated or “killed” virus (KV) is a “classical approach that has produced safe and effective human and veterinary vaccines but has received relatively little attention in the effort to develop an HIV/AIDS vaccine. Initially, KV and rgp120 subunit vaccines were the two most obvious approaches but, unfortunately, rgp120 has not been efficacious and the KV approach has been limited by a variety of scientific, technica Read More

One major obstacle to the design of a global HIV-1 vaccine is viral diversity. Presently, data suggest that a single antigen will not suffice to generate broadly reactive neutralizing antibodies to protect all individuals against all subtypes of HIV-1 infection. While some of the neutralizing epitopes are identified in the constant regions of the HIV-1 envelope (Env) glycoprotein, many are localized to variable regions and differ conformatio Read More

The development of an effective vaccine against HIV-1 would be greatly facilitated by the ability to elicit potent, high affinity antibodies that are capable of broad neutralization, viral inactivation and protection against infection and/or disease. New insights into the structure and function of the HIV-1 envelope glycoprotein (Env) that mediates viral fusion and entry may ultimately lead to strategies successful in eliciting these prot Read More

Transmission of human immunodeficiency virus type 1 (HIV-1) selects for envelope variants with a number of defined properties, including use of CCR5 as the preferred coreceptor, binding to CCR5 in a distinct manner compared to HIV-1 isolated later in infection, shorter variable (V) regions, and fewer N-linked glycosylation sites. These features define the ideal target for an envelope-containing vaccine designed to elicit neutr Read More

Current HIV vaccines in development appear unlikely to prevent infection, but could provide benefits by increasing survival; such vaccines are described as disease-modifying vaccines. We review the current status of vaccines and modeling vaccines. We also predict the impact that disease-modifying vaccines could have in South Africa, where multiple subtypes are co-circulating. We model transmissibility/fitness differences Read More

Since the discovery of simian immunodeficiency viruses (SIV) causing AIDS-like diseases in Asian macaques, non-human primates (NHP) have played an important role in AIDS vaccine research. A multitude of vaccines and immunization approaches have been evaluated, including live attenuated viruses, DNA vaccines, viral and bacterial vectors, subunit proteins, and combinations thereof. Depending on the particular v Read More