HIV Vaccine Development Faces Several Scientific Obstacles, Fauci Says in Opinion Piece
Although it is a "very reasonable query" to wonder why the scientific community has not developed an HIV/AIDS vaccine, research on developing such a vaccine has faced many scientific obstacles, Anthony Fauci, director of NIH's National Institute for Allergy and Infectious Diseases, writes in an MSNBC.com opinion piece. According to Fauci, scientists successfully have been able to develop vaccines for other diseases using a "proof of concept," which provides a "reasonably reliable" measure of the body's capacity to mount an effective immune response to an illness. Although the first attempts to develop an HIV vaccine followed this approach, these vaccines were ineffective because HIV "has never provided scientists with a proof of concept of predictable protection," Fauci writes. He continues, "Not a single individual is known to have spontaneously eradicated the virus," adding that for most people not taking antiretroviral drugs, HIV progression is "relentless, despite measurable, but apparently not completely adequate, HIV-specific immune responses."
According to Fauci, several factors account for the "inadequacy" of immune responses to HIV, including the virus' ability to establish latency and "hide" in host cells; its capacity to adapt and mutate; its ability to avoid immune responses; and its capacity to destroy or disable critical immune system cells. Fauci writes that considering these obstacles, HIV researchers "must learn how to prompt the human body to produce a protective immune response that is superior to that elicited by natural infection." In addition, HIV's ability to disseminate rapidly in the body following transmission requires vaccine researchers to "devise a vaccine that elicits an immune response that acts quickly to destroy the virus or learn how to extend the 'grace period'" between transmission and infection, Fauci writes.
According to Fauci, individuals in very rare circumstances have developed antibodies that neutralize HIV in the body, so it is "at least theoretically possible" to induce a similar immune response using a vaccine. In addition, "manipulating the innate immune system might alter the course of infection, perhaps widening the window of opportunity for viral eradication before HIV establishes an intractable reservoir of virus," Fauci writes. He continues that improved knowledge of the earliest stages of HIV could "lead to other strategies that extend the 'grace period' and allow the immune system time to more effectively respond." Finally, research on "elite controllers" -- HIV-positive people who do not progress to AIDS for several years or decades -- may provide a "different sort of 'proof of concept,'" Fauci writes. He continues that although "developing a vaccine capable of preventing infection is the ultimate goal, development of a vaccine that enables the recipient to control infection for years to decades would delay the need to initiate antiretroviral therapy and potentially even reduce secondary transmission to others."
Fauci writes that HIV vaccine development might never follow the path of earlier vaccines, and therefore "our efforts in HIV vaccinology must be part of a broader approach toward HIV prevention that includes the delivery of proven methods," including HIV testing, counseling, education, behavior change programs, condom distribution, drug and alcohol abuse prevention, needle-exchange programs, prevention of mother-to-child HIV transmission and male circumcision. Furthermore, new interventions such as topical microbicide gels and pre-exposure prophylaxis are undergoing "advanced testing," Fauci writes. However, he continues that "the development of an HIV vaccine must remain at the top of the global health research agenda." He concludes, "The obstacles to success are scientific obstacles, and I am cautiously optimistic that we will overcome these obstacles with scientific solutions, so there is no longer a need to ask the question: 'Why do we not yet have an AIDS vaccine?'" (Fauci, MSNBC.com, 3/31).