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State of Current AIDS Vaccine Research :
Reproduced with permission from (International association of vaccines and Immunology)

LEFT : Electron microscopic image of HIV viruses. Note the dark core and comparitively lighter periphery. Click on the image for a larger picture.

You might find it useful to review the structure of the HIV virus (click here) before continuing.

            Given the scale of the AIDS pandemic and the long lead time required for development and distribution of an AIDS vaccine, the number of products now in clinical testing is woefully inadequate. After more than 15 years of research on HIV, only one vaccine concept is being tested for efficacy in and only one other type of vaccine has entered Phase II trials. Equally serious is the shortage of vaccine candidates currently undergoing Phase I trials, the necessary precursors to the later tests.  Although there are different designs that might lead to a useful AIDS vaccine, most of them have in common that they use specific parts of HIV (genes or proteins) to activate the body's immune defenses. Once the immune system has learned to recognize these viral components, the hope is that it can mount a vigorous defense when it encounters the real virus.  The following list summarizes the different concepts currently being tested as candidate AIDS vaccines. 

1) Recombinant subunit vaccines:
introduce a harmless subunit (portion) of an HIV protein into the body. This is the basis of AIDSVAX, the first vaccine being tested for effectiveness in humans and which is made from a portion of HIV's outer surface (envelope) protein, called gp120. The hepatitis B vaccine successfully uses this approach to confer protective immunity. 

Candidate recombinant subunit vaccines for AIDS in clinical trials:  gp 120: Phase III p24: Phase I

2)DNA vaccines:
 also known as "naked DNA" or "nucleic acid" vaccines, use the actual genes of HIV as a vaccine. Once introduced into skin or muscle, the genetic material is taken up by cells in the body, which then produce HIV proteins that stimulate the immune system. Several experimental vaccines s using this new technology against other diseases have successfully protected animals, including experimental SIV vaccines in monkeys.

  Current status of DNA vaccines for AIDS in clinical trials: Phase I 

3)Live recombinant viral vector vaccines:
are created by genetically engineering relatively harmless, replicating viruses to produce HIV proteins, which then stimulate HIV-specific immune responses. Many HIV vaccine candidates now in development are made with some type of viral vector. These include the alphavirus vectors (Venezuelan Equine Encephalitis; Sindbis or Semliki Forest viruses); adenovirus; adeno-associated virus (AAV); and pox viruses (e.g. canarypox; fowlpox, modified vaccinia Ankara [MVA] and vaccinia). Despite this significant preclinical activity, only two viral vector strategies have thus far reached clinical trials. One of them, the canarypox-based vaccines, may be the next concept to reach large-scale efficacy trials.

 Candidate live recombinant viral vector vaccines for AIDS in clinical trials:  Canarypox: Phase II Vaccinia: Phase I

 4)Live recombinant bacterial vector vaccines
are similar in concept to viral vector vaccines, except that the HIV genetic material is molecularly engineered into bacteria rather than viruses. Potential advantages are that this type of vaccine can usually be produced cheaply, and that it can be given orally rather than injected. Several bacterial systems are currently being evaluated for their potential as AIDS vaccines. These include Salmonella, Shigella, Listeria, and BCG.

  Candidate live recombinant bacterial vector vaccines for AIDS in clinical trials:  Salmonella: Phase I

5)Live-attenuated vaccines
are used globally against many viral diseases, such as polio (Sabin vaccine) and measles. They consist of weakened (attenuated) but living virus that is too disabled to cause disease but can still infect cells and replicate within the body. By learning to respond to weakened virus, the immune system can then protect against the full-strength, disease-causing strain. In monkeys, live-attenuated SIV vaccines have proven to induce protective immunity against SIV far more consistently than any other type of vaccine. Safety is a serious concern, however, because of well-documented instances of AIDS occurring in a small percentage of monkeys inoculated with certain strains of live-attenuated SIV vaccines. 

Candidate live-attenuated AIDS vaccines in clinical trials:

6)Whole-inactivated vaccines
are used worldwide against many viral diseases, including polio (Salk vaccine), hepatitis A and influenza. The advantage of this approach is that it presents the entire viral particle to the immune system, which therefore "sees" the full spectrum of viral proteins. Yet the virus cannot infect and replicate, making this a safer approach than live-attenuated strategies. But for a variety of reasons, including some technical difficulties, it has not been widely pursued for HIV. 

Candidate whole inactivated AIDS vaccines in clinical trials:

7)Virus-like particle vaccines
are made by using several different HIV proteins engineered to mimic an HIV particle. Studies have shown that these incomplete viral particles can stimulate both antibody and cellular immune responses, and are safe and immunogenic. 

Candidate virus-like particle vaccines for AIDS currently in clinical trials:

8)Synthetic peptide vaccines
consist of very small portions of HIV proteins chosen specifically to focus the body's anti-HIV immune responses on what are thought to be the most potent immunity-inducing regions of the proteins. Extensive basic research has shown that the immune system will mount a response to certain very short protein segments (called peptides) when these peptides are displayed appropriately to the immune system. 

Candidate synthetic peptide vaccines for AIDS in clinical trials
  p17: Phase I Lipopeptides: Phase I V3-based: Phase I 

9)”Jennerian" vaccines:
In the 18th century, Edward Jenner discovered that immunization with cowpox protected people against variola virus, the cause of smallpox in humans. This concept of "Jennerian" vaccines, based on using similar but non-identical viruses to those that cause disease, is being explored for HIV. Possibilities include the simian equivalent of HIV (called SIV); a weaker strain of HIV called HIV-2; and lentiviruses from other species, such as the caprine arthritis encephalitis virus (CAEV). 

10)Complex vaccines
attempt to direct immune responses to the human host cell receptors that serve as HIV's port of entry into cells, rather than to HIV itself. The idea is that by blocking HIV receptors (such as the CD4 or CCR5 molecules), virus will be unable to attach to the cell surface or to infect cells.

Candidate Jennerian or complex vaccines in clinical trials: NONE 

11)Combination vaccines:
use two or more of the above approaches, based on the premise that this could induce a broader spectrum of immune responses than any single approach. One combination now in phase II trials uses a canarypox viral vector together with a gp120 subunit from HIV's outer surface. Another combination strategy uses a DNA vaccine to "prime" the immune system and an MVA vaccine to "boost."

Current status of combination vaccines for AIDS in clinical trials: Canarypox + gp120: Phase II