Immunization, Vaccines and Biologicals

HIV vaccine development

Background and challenges

AIDS vaccine development is complex. First attempts to develop a vaccine against HIV in the late 1980s were based on eliciting an antibody response, which is how most vaccines are thought to work. However, because HIV mutates rapidly, and its outer spike protein conceals itself from the immune system, creating the appropriate viral antigens to use in a vaccine proved remarkably difficult, and the approach was abandoned. More recently, many scientists believe that an AIDS vaccine candidate will provide robust protection against HIV infection only if it engages both arms of the adaptive immune system, i.e. cell-mediated and antibody-based immune responses.

HIV vaccine development is complicated by the incredible variability of the virus, and in particular its envelope protein at both the individual and population level. Thus, the evolving number of virus subtypes and recombinations renders vaccine development targeting the viral envelope constituents very difficult. Consequently, vaccines may have to be carefully adapted to the virus forms in circulation in the precise location where their use is intended.

Clinical trials

Encouragingly, data from the first HIV vaccine trial to show a positive protective signal were released in 2009. The trial, termed RV 144, was performed in Thailand. It used a combination of two vaccines in a heterologous prime-boost paradigm, i.e. one vaccine given in four doses was then "boosted" by two doses containing both vaccines. Analysis of the trial showed that the group receiving the vaccine had an infection rate 31.2% lower than the group that received the placebo. Although this result is not enough to qualify the vaccine for licensure, RV144 has provided very useful pointers for a way forward. Several trials are planned incorporating lessons from RV 144. If the required efficacy can be shown in any of the trials, an HIV/AIDS vaccine could become available from 2020.

The role of WHO

The Initiative for Vaccine Research (IVR) works through the joint WHO-UNAIDS HIV Vaccine Initiative to accelerate the availability of a safe, effective and affordable HIV vaccine as follows:

  • Building international consensus, inter alia, on: assays to evaluate the safety and immunogenicity of vaccine candidates; endpoints to determine clinical efficacy; standards for vaccine evaluation and quality control; clinical trial design, clinical development plans and regulatory pathways; target product profiles; and research ethics and community participation in biomedical HIV prevention trials.
  • Building the capacity of regulatory agencies in disease endemic countries to evaluate HIV vaccine-related submissions for clinical studies and eventually licensure.
  • Supporting HIV high burden countries to define a national strategy for the evaluation of, and access to new HIV vaccines.
  • Assuring that HIV vaccine clinical trials collect all information necessary for a future WHO policy recommendation.

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