Thursday, 09 October 2008 11:47

Ten Kenyans hold Key to an HIV Vaccine

Written by Arthur Okwemba

HIV/ AIDSLocal scientists have managed to identify 10 HIV positive Kenyans with an antibody that could hold the key to developing an effective AIDS vaccine.

The individuals, who the scientists say have powerful antibodies that neutralise the virus, stopping it from infecting new cells, have neither used any antiretroviral drugs nor been attacked by opportunistic infections despite living with the virus for over nine years.

On being screened, the individuals were found to possess high CD4 count- immune cells used to fight infections- and very low viral loads-amount of HIV in the body-, which were uncharacteristic of an infected person.

They also have very low possibilities of transmitting the virus to another individual as well as being able to delay progression to AIDS, the last stage of the disease where opportunistic infections reign, killing the individual if not well managed.

This means if a vaccine that elicits these antibodies is developed; it would significantly cut down on the number of new infections in Kenya and other HIV hotbeds.

The 10 individuals are now being followed to establish who among them qualify to be what scientists refer to as Elite Controllers-individuals who are able to control HIV viral load to less than 50 copies compared to over 30,000 copies of HIV in a person without such antibodies.

“This new phenomenon is being seen in both men and women who we have screened in Nairobi, and we are keenly following them to identify the key antibodies that make them tick,” says Prof Omu Anzala, the Director of Kenya Aids Vaccine Initiative.

Disclosing the findings, Prof Anzala said those screened so far have an immune system able to elicit antibodies – CD4 and CD8- with a unique protein that target specific sites of HIV stopping it from infecting new cells.

{styleboxjp echo=yes}In Africa, of the 1,700 HIV positive people who been screened in the past one year, 170 have HIV neutralising antibodies. Kenya, Uganda, Rwanda, South Africa, and Zambia, are some of those marked to help in solving this problem.{/styleboxjp}

“What we are experiencing now is phenomenal and provides critical information of how we move forward and the massive work we need to undertake in this direction,” says Dr Wayne Koff, of International Aids Vaccine Initiative (IAVI).

In interview, Wayne said they have managed to identify four antibodies with ability to neutralise the virus and are currently studying them to see which ones are broadly neutralising-those with ability to neutralise different types of HIV strains such as A, B, C and D.

In this quest, they are also paying particular attention to immune systems of individuals who have lived with HIV for the past three years without using ARVs. Some of them are believed to possess the neutralising antibodies.

Buoyed by these new findings, IAVI is going to set aside between 30 and 50 per cent of its budget on vaccine discovery on the identification and development of a vaccine with the ability to elicit broadly neutralising antibodies, according to Dr Koff.

Likewise, IAVI has developed what they call Protocol G, whose sole objective is to help scientists identify elite controllers across Africa and other parts of the world.

Identifying the broadly neutralising antibodies and then using the knowledge to develop a vaccine to produce similar responses in HIV negative individuals has been the most difficult thing for scientists. It has taken them over 10 years to just understand this phenomenon well.  

Speaking recently in Nairobi to a group of scientists from Africa, Dr Koff admitted that “as a field we have not understood as yet how to elicit broadly neutralising antibodies to tackle HIV.”

“But now,” adds an elated and optimistic Prof Anzala, “we are on the path to somewhere and can see light at the end of the tunnel.”

The closet the scientists came to generating neutralising antibodies was during the Vaxgen vaccine trials. It never worked as the vaccine failed to elicit such antibodies in amounts necessary to control HIV infection.

Still, there other challenges even with the new discovery. The four neutralising antibodies identified so far work on just one site of HIV, when they are need to do so on various points to be able to disable it effectively. Consequently, the search is now on to find other antibodies that work on different sites of the virus.

Discovery of these antibodies will help the scientists develop a vaccine with the ability to disable a wide range of HIV strains such as A, C, and D, which are circulating in Kenya.

As for now, the four antibodies discovered are crucial since unlike the cellular immune response that destroys a cell once infected and on which past vaccines have been developed; the neutralising antibodies are able to prevent the virus from infecting the cell in the first place.

Studies in the primates have already shown that broadly neutralising anti-bodies to possess the ability to prevent infection.

This encouraging information has led scientists to establish Neutralising Antibody Consortium, whose sole responsibility is pick-up more antibodies with ability to prevent HIV infection. Formed in 2002, the Consortium has grown from four academic institutions to 18 now. 

But as they undertake all these initiatives, scientists believe a vaccine that produces both broadly neutralising antibodies and cellular immune response would be the most effective one in controlling the virus.

Cellular immune response is where the immune system cells identify and kill the infected CD4 cells.  These two approaches are going to require massive investment as well as facing numerious challenges.

In its AIDS Vaccine BluePrint 2008: A Challenge to the Field, A Road Map for Progress, IAVI is acutely aware of this fact.

IAVI admits that the virus remains difficult to contain because of its HIV immune evasion mechanisms, is sexually transmitted, and has high capacity of recombination, among others.

To tackle these challenges, the Blueprint recommends the following roadmap:

  • Determine the mechanisms responsible for control of HIV infection by elite controllers.
  • Provide incentives to companies in this field as away of enhancing innovation in AIDS vaccine discovery and development.
  • Build capacity of scientists and countries to conduct clinical trials.
  • Train the next generation of HIV scientists.
  • Trim the product development pipeline of less promising vaccines candidates and those with low probability of success. These resources should then be redirected towards more promising approaches or in solving key scientific challenges.
  • Sustain and enhance financing for AIDS vaccine research and development.
  • Establish a mechanism to monitor progress in the AIDS vaccine field.
  • Determine the mechanism responsible for control of SIV infection by live-attenuated SIV.
  • Implement a new clinical research program to determine the optimal immunogens for eliciting cell-mediated immunity.

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