Developing a vaccine against HIV: Where we stand

Background information:

Vaccines are biological substances that induce the immune system to create antibodies against disease causing agents (antigens).

There are two main methods of creating vaccines:

  1. The use of live attenuated organisms

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or “live”). Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent (virulent= poisonous/ toxic/ extremely severe or harmful in its effects).

  1. The use of killed/ inactivated organisms

The following link provides a simplified introduction to vaccine production:

Vaccines are prepared from stable strains/ variants of the pathogen (disease causing organism). This works well for many diseases, since they don’t change very much.

The Problem with HIV

  1. The Human Immunodeficiency Virus (HIV) is a difficult candidate for the creation of a vaccine because it tends to mutate (undergo genetic changes) very often. So, there are numerous variants of HIV.
  2. Quickly following transmission, the virus spreads and establishes a persistent infection, including hidden reservoirs from which it can strike again at any time.
  3. While some individuals do develop antibodies against the virus, they do so only after many years of infection. Moreover, this phenomenon occurs in about 25% patients only. By the time these antibodies appear, the virus has already caused considerable damage.

Possible Approaches

  1. Researchers generally agree that an ideal HIV vaccine would induce the production of so-called broadly neutralizing antibodies, which are capable of neutralizing a broad swath of HIV strains and are produced naturally by approximately 25 percent of chronically HIV-infected people.
  2. Boost the immune system/ the immune response against HIV.

Introduce an HIV antigen that induces cellular immune responses against HIV

  1. Bypass the immune system

Direct injection of HIV-neutralizing antibodies

Current situation

  1. Development of Broadly Neutralizing Antibodies

Researchers have identified a structure-based HIV vaccine design approach as the most promising. Using a similar approach, they have managed to develop a candidate vaccine against paediatric respiratory syncytial virus (RSV).

An atomic level image of the HIV envelope trime, the main target for the broadly neutralizing antibodies, has been obtained in 2013.

Scientists are now attemtpting to create immunogens that mimic the structure of the trimer. One group has developed a computationally derived HIV immunogen that can bind multiple broadly neutralizing antibodies and their precursors.

  1. Boosting the immune response

Researchers have received a modest clinical signal that using two vaccines in succession could reduce the rate of HIV infection. How this was achieved, however, is still under study.

Some researchers are designing so-called mosaic antigens to overcome HIV diversity. These are computationally derived proteins created by stitching together genetic sequences from across the entire HIV genome.

  1. Bypassing the immune system

Phase I trials are underway to test this approach.


Efforts to develop a vaccine against HIV are directed along a few main approaches:

Develop broadly neutralizing antibodies

Boost immune response/ system

Bypass the immune system

The most promising approach at present is that attempting to stimulate the production of broadly neutralizing antibodies.

Passive immunization strategies are undergoing Phase I trials.

Useful links:

Link to International AIDS Vaccine Initiative (IAVI) press release dated 18 June 2015:

Link to Scientific Article on recent developments in the journal Cell Reports 28 April 2015 (Open Access) Warning: Highly technical:

Click to access S2211-1247(15)00326-5.pdf

Link to article in The Scientist explaining the status of HIV vaccines (‘Defeating the virus’):

Link to the IAVIReport Issue I (2015), discussing the HIV Trimer and recent developments Warning: Highly Technical:

Click to access IR_Vol19No1_2015.pdf

Link to the web site of IAVI:

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