Human immunodeficiency virus vaccines

Abstract

Although some success was achieved in recent years in HIV prevention, an effective vaccine remains the means with the most potential of curtailing HIV-1 infections worldwide. Despite multiple failed attempts, a recent HIV vaccine regimen demonstrated modest protection from infection. Although the protective efficacy in this trial was not sufficient to warrant licensure, it spurred renewed optimism in the field and has provided valuable insights for improving future vaccine designs. This review summarizes the pertinent details of vaccine development and discusses ways the field is moving forward to develop a vaccine to prevent HIV infection and disease progression.

Keywords: Binding antibodies; DNA prime; HIV vaccines; Neutralizing antibodies; Protein boost; T cells; Viral vector.

Fig. 1

Adaptive immune responses. The adaptive arms of the immune system are composed of the humoral (antibody) and the cellular (T-cell) -mediated immunity. (top) Naïve CD4⁺ T cells can differentiate into follicular helper CD4⁺ T cells (T_FH) or type 2 helper T cells (Th2) that are involved in B-cell activation following antigenic stimulation. Through the interaction of CD40 on B cells with CD40L on CD4 T cells, B cells will then differentiate into plasma cells, which will produce antibodies against HIV, thus preventing the virus from infecting target CD4 T cells. (center) Naïve CD4⁺ T cells differentiate into type 1 helper T cells (Th1) that can activate HIV-specific CD8⁺ T cells through the CD40/CD40L interaction. Activated CD8⁺ T cells mediate the killing of HIV-infected target T cells through the release of effector cytokines and molecules. (bottom) Naïve CD4⁺ T cells can differentiate into cytolytic CD4⁺ T cells, which can directly kill infected targets. IFN-γ, interferon-γ; IL, interleukin.

Fig. 2

Clade-specific HIV-1 immunogens and their delivery vehicles used in the vaccine regimens tested for efficacy. The HIV-1 clades from which the immunogens were derived, the type of immunogen used, and the mode of vaccine delivery are shown for each of the 4 vaccine regimens. At the center is a simplified depiction of an HIV virion showing the major proteins used as immunogens. ^a The bivalent clade B vaccine used in the VaxGen USA trial consisted of Env proteins from the MN and the GNE8 strains.

Fig. 3

Safety and efficacy of the 4 HIV vaccine studies. The timeline for each of the 4 vaccines is shown in terms of which year any given trial started^a and ended^b. The specific arms of the adaptive immunity measured are shown for each study. In addition, the safety and efficacy findings for each trial are summarized.