In a lecture on March 21 to College students and faculty, National Institute of Health (NIH) Vaccine Branch researcher Marjorie Robert-Guroff, Ph.D., discussed the history, vaccine trials, and treatment roadblocks of Human Immunodeficiency Virus (HIV), the causative agent of AIDS, in her lecture “Developing Vaccines for HIV/AIDS: Challenges and Prospects.”
AIDS, or Acquired Immune Deficiency Syndrome, is a disease characterized by a low population of CD4 T-lymphocytes (more commonly known as Helper T Cells) in the body, which prevents the body’s immune system from protecting against pathogenic infection and disease. The mysterious disease was first classified in California men in 1981. By 1983, HIV was discovered in patients with similar symptoms, and by 1984, HIV was officially recognized as the etiologic (causative) agent of AIDS.
“As of 2010, 34 million people were living with HIV,” said Robert-Guroff, “with 7,000 new infections a day that year.” While only 1.3 million of that annual infected population reside in North America, some cities in the United States show particularly high prevalence (e.g. 3 percent in Washington, D.C.), making the issue more than a Sub-Saharan African problem.
Said Robert-Guroff, “There’s been an intervention for achieving an AIDS-free generation.”
Since these efforts, HIV transmission has been reduced by 96 percent through anti-retroviral therapies (therapies against retroviruses like HIV), including a 75 percent decrease in perinatal transmission since 1992. However, these facts show support of treatment as a method of prevention, and do not exemplify the many problems behind HIV vaccine development that Robert-Guroff discussed.
“Challenges behind developing an effective HIV vaccine include the need to elicit sterilized immunity,” said Robert-Guroff. For vaccine developers, this means developing a reagent that can stop HIV from entering lymphocytes, where they can replicate, destroy the cell, and continue to infect the body’s immune cells.
A problem behind doing this with a HIV particle is the complexity of its outer shell, or sugar-protein coat. The GP41 (or “spike”) receptor that aids in HIV’s entry into a cell is a very possible target for HIV vaccines, but the shape of the coat creates steric hindrance that prevents most tested reagents from being able to reach GP41 to bind to it.
“A special kind of antibody is needed to bind to the virus,” said Robert-Guroff.
Other issues behind vaccine development include viral variability, viral mutability, and immune escape. There are eight groups, or clades, of HIV viruses that each differ to a significant extent from each other. This most likely prevents a vaccine developed for one group to be effective against another group. While HIV clades are mostly region-based, with the United States HIV cases mostly being clade B and Subsaharan Africa being mostly clade C, this further complicates HIV vaccine research by preventing worldwide focus on one structure of virus.
Furthermore, as a RNA-based retrovirus, HIV has a high mutation rate that prevents one treatment from working effectively in the long-term. As one treatment prevents replication of one HIV type (strain), that strain mutates so that it can still reproduce but no longer be targetable by the original vaccine. This has been one of the more frustrating elements of vaccine development, leading to HIV’s ability to avoid the immune response (viral escape).
To counteract this, researchers began targeting regions of the virus that, due to their vital and specific structure, would remain fairly constant even in multiple HIV strains (meaning that even if the virus mutated, the vaccine would still be effective). However, most of these regions are in indents, or pockets, of the virus that offer steric hindrance, preventing vaccine particles from targeting the sites.
Other roadblocks include HIV’s function as an infector of mucosal epithelia (a route of infection for which not many vaccines are currently available) and the lack of small animal models (like mice) for HIV infection. Having these models would allow for more effective and faster research, but without them, researchers are limited to monkey and, until recently, chimpanzee models that show slow, non-pathogenic behaviors of HIV and are extremely expensive, not to mentioned ethically questioned.
Vaccine development, however, has not been at a standstill. Two major human trials, including the STEP Trial in 2007 and the RV 144 Trial in 2009, changed how researchers in the field approached the problems of vaccine development. While the 2007 trial failed to stimulate CD8 T-lymphocytes (or “killer T-cells”) to attack the virus, the subsequent 2009 trial prevented HIV transmission in 31.2 percent of tested patients. While vaccines ideally prevent more than 90 percent of transmission, this was nevertheless a milestone in understanding effective vaccine development for the virus.
After a discussion of the successes behind RV 144 and strategies for developing different types of vaccines, she concluded with the main goals of the vaccine.
“For a vaccine, we want neutralizing antibodies,” said Robert-Guroff, referring to proteins designed by the human body that would specifically bind to HIV and stop it from entering human cells. She also discussed how an effective vaccine would create multiple immune responses to HIV infection, including immunity at the cellular, humoral, mucosal, and innate levels.
“Overall, I’m optimistic,” she said, “but it’s a long road. We’re not close yet, I think.”
The lecture seemed to be well-received by the audience of science and non-science majors and faculty. “I liked her in-depth discussion of vaccines, and how she was able to say we’re really not close to a cure yet,” said senior Biology major Michael Adashek.
The lecture was held at 4:45 p.m. in Cole Cinema as part of the Thirteenth Annual Women, Gender, and Sexuality Studies Colloquium.