SADANAND: Next step in battle against AIDs: a good vaccine

For the last 24 years, the world has observed World AIDS Day on Dec. 1st, a day to raise awareness about AIDS and reflect on the progress made and future initiatives in fighting the disease. This year there is a lot to be proud of. The Joint United Nations Program on HIV/AIDS (UNAIDS) released a report ahead of World AIDS Day that included some striking results – infection rates have dropped by more than 50 percent in 25 low-and middle-income countries and, in comparison to 2001, there were 700,000 fewer new infections.

Importantly, dramatic infection rate reduction has been seen in the worst-affected region of the world, sub-Saharan Africa. The report suggests that, incredibly, one of the ambitious Millenium Development Goals may in fact be achieved by 2015 – the successful combatting of AIDS. The progress in fighting AIDS has been achieved through a multi-pronged strategy that involves significant investment in and distribution of antiretroviral treatment, promotion of testing — particularly amongst the oft-stigmatized populations that disproportionately suffer from AIDS -— and promotion in non-drug based preventative measures and education. Fairly simple things — for example, circumcision — have been found to dramatically reduce the AIDS transmission rate. The UNAIDS report was extremely promising, but the Holy Grail in the fight against AIDS remains the discovery of an effective vaccine. No disease can be eradicated or thoroughly limited without a broad vaccination campaign.

All vaccines (that are currently on the market) lead to the generation of neutralizing antibodies, secreted proteins that can bind specific parts of the pathogen, thereby targeting the pathogen for destruction and preventing them from infecting cells should we be exposed to the pathogen in the future. However, HIV replicates and mutates incredibly fast — it is estimated that it mutates as much in one day as the flu virus does in a year — and this is why it has been such a problematic vaccine target. HIV-infected individuals can harbor many genetically different HIV strains, so unless a vaccine can elicit broadly neutralizing antibodies — antibodies that can effectively stymy many distinct HIV strains — it will not be useful in preventing infection for everyone. Identifying neutralizing antibodies is not easy; the work involves repeatedly screening many patients in order to evaluate not only the antibody repertoire but also the virus variants the patients have.

This past October, a study was published in Nature Medicine that defined a new, susceptible HIV variant in two patients. The two patients had antibodies that recognize a spot on the virus shell, a hitherto unknown vulnerability generated by a single shift in one sugar-like molecule that was inaccessible to antibodies in the initial virus infection but emerged in a virus variant several months later. By identifying broadly neutralizing antibodies that currently exist in patients, researchers ultimately hope to generate vaccines that can induce production of these antibodies, limiting the ability of HIV to take hold in exposed individuals. There are no guarantees; past vaccine trials have ended in disappointment and the high-profile Merck vaccine trial that ended a few years ago is even believed to have made some immunized individuals more susceptible to HIV infection. However, the identification of a broadly neutralizing antibody and its virus binding site is a significant development because it sheds light on how the virus can be thwarted as it evolves, providing a therapeutic target as well as a protective target.

There is a lot to be hopeful about in the ongoing fight against AIDS, but there is still work to be done. Since AIDS is a chronic disease, antiretroviral treatments will continue to be important for many millions of people. Even if we did have an effective vaccine against HIV, we might still not achieve disease eradication for some time — polio, a disease that could have been eradicated years ago, still lingers in certain pockets of the world due to distrust of and infrastructure limits to vaccination campaigns. However, a successful vaccine would have an immediate impact in reducing transmission of AIDS and hopefully making it a thing of the past within the next century.

Contact Saheli sadanand at saheli.sadanand@yale.edu .

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