Max Essex

In introducing Essex, HSPH Dean Barry Bloom and Harvard AIDS Institute Executive Director Ric Marlink emphasized Essex’s practice of applying laboratory science to real-world problems. Said Dean Bloom, "After an extremely cutting-edge distinguished scientific career, [Max Essex] did something really quite remarkable. He got directly involved in a problem in the real world," helping to train individuals who have become leaders in AIDS research in countries all over the world.

The global HIV/AIDS epidemic is overwhelmingly concentrated in sub-Saharan Africa–home to 67 percent of the 40 million HIV-infected people worldwide in 2003. The region is also where nearly 70 percent of new infections and 77 percent of AIDS-related deaths occur. Scientific efforts to tackle HIV therefore should concentrate on solutions that will be meaningful in Africa, as well as in Western countries, asserted Essex. Bridging the needs of the two regions is deeply challenging.

The virus that causes AIDS has evolved into two distinct types, HIV-1 and the less virulent HIV-2. A group of researchers that included Essex and Phyllis Kanki, professor of immunology and infectious diseases in the Department of Immunology and Infectious Diseases, provided the first evidence for HIV-2.

Within the classification of HIV-1, there are several subtypes and recombinants, or hybrids. Subtype HIV-1B is common in the West. Subtype HIV-1C, a particularly virulent form, plagues sub-Saharan Africa. A region of the world dramatically ill-equipped to handle infectious disease outbreaks has been afflicted by one of the most easily spread forms of the AIDS virus.

One hypothetical explanation for why HIV-1C appears to spread faster than other subtypes is that the virus may be able to transcribe its RNA–and therefore replicate–faster than other forms, explained Essex.

With the plethora of subtypes, vaccine development becomes exceptionally difficult. HIV possesses an astonishing mutation rate. One infected person can produce billions of mutants a day. Many of these mutated forms of the virus will not survive to replicate themselves, but others will successfully reproduce. The body’s immune system cannot keep up.

Explained Essex, "The neutralizing antibody [produced by the immune system] might very effectively neutralize the virus clone that was [dominant] in your body last week, but will not neutralize the newly emerging variant."

Further evading the immune system, HIV can hide within the body’s chromosomal DNA. The immune system may investigate a cell hiding HIV and never detect the presence of the lurking virus.

As if those evasive characteristics were not enough, HIV attacks and hijacks the very cells of the immune system meant to defeat the virus.

Currently, there are a few companies vigorously pursuing an HIV vaccine, according to Essex. A problem with many of the development programs is that they use HIV-1B as a target, and it is unclear whether a successful vaccine for HIV-1B will work against HIV-1C, the subtype most common in sub-Saharan Africa, he said.

With the government of Botswana and with U.S. partners, HAI has undertaken a Phase I HIV vaccine trial at several sites of a candidate vaccine called EP HIV-1090, developed by the California company Epimmune. The candidate is a DNA vaccine using a polyepitope design, where only the fragments of HIV known to stimulate immune responses are included. Theoretically, the design should allow researchers to adjust the vaccine to target specific subtypes of HIV. The vaccine trial arm in Botswana is now fully enrolled, said Essex. The preliminary results suggest that the vaccine is safe, but that modifications will probably be necessary to match the vaccine components to the genetics of the population.

Residents of Botswana once enjoyed the highest life expectancy in Africa: 73.2 years, said Essex. With the advent of AIDS, life expectancy in Botswana for the year 2010 has plummeted to a projected 29 years.

Said Essex, "One of the clearest and most emphatic messages here is about what the impact will be if we don’t do something [more]." A vaccine may be part of the answer. "I am very optimistic that we will have a protective vaccine in the future, but the development of such a tool may take many years," he said.

A webcast of the talk is available at http://www.hsph.harvard.edu/live/Essex2.html.

--CC