An international research team has developed a vaccine that provides some protection for monkeys against the simian immunodeficiency virus (SIV), and the discovery may light the path to a vaccine candidate that will protect humans from HIV.
The research demonstrates that “scientists are homing in on the critical ingredients of a protective HIV vaccine,” according to an announcement January 4 by Harvard University, which is among the supporters of the Ragon Institute, an institution expressly created in 2009 to bring fresh approaches to the pursuit of a vaccine against HIV, the virus that brings on AIDS.
The U.S. Military HIV Research Program (MHRP), Beth Israel Deaconess Medical Center (BIDMC) and the pharmaceutical company Crucell Holland B.V. were also partners in the collaboration. The National Institute of Allergy and Infectious Diseases (NIAID) joined the other institutions in providing backing for the work.
This is the first research effort to show partial vaccine protection in a test with animals, and it also demonstrated that novel combinations of different vaccines — rather than a single vaccine alone — administered to rhesus monkeys can achieve that protection. Monkeys don’t develop disease when exposed to HIV, so closely-related SIV offers the best testing ground for a vaccine that might ultimately be administered to humans.
The group used a “prime boost” vaccine technique developed over the last decade that involves a two-stage immunization process, administering different vaccine formulas several months apart. After they administered a second vaccine, the “boost,” the researchers injected the monkeys with SIV.
This regimen resulted in a more than 80 percent reduction in the per exposure probability that the monkeys would become infected.
“This study allowed us to evaluate the protective efficacy of several prime-boost vaccine combinations,” said Dr. Dan H. Barouch of BIDMC, “and these data will help guide the advancement of the most promising candidates into clinical trials.” As BIDMC’s chief of vaccine research, Barouch led the study.
The researchers also analyzed the type of responses mounted by the monkeys’ immune system. They found that animals produced different antibodies in response to each of the vaccines administered. Attacking the SIV cells differently, these antibodies achieved their most significant level of protection when monkeys’ immune systems mounted defenses against both the envelope protein that makes up the outer coat of SIV and the virus’s capability to replicate after infecting the host.
Those distinctly different immune system responses “likely reflect fundamentally different requirements to block establishment of infection compared with controlling viral replication after infection,” said Colonel Nelson Michael, director of the U.S. MHRP at Walter Reed Army Institute of Research.
These findings produce enough positive evidence to push the research to the next phase, according to statements by the partners. The collaborators plan to move to the first phase of clinical testing in which vaccine candidates will be administered to humans at trial sites in the United States, East Africa, South Africa and Thailand. Participants in the research still caution that results in animal testing cannot be projected forward as an outcome of future human testing. Medications always must move through three phases of clinical testing for both efficacy and safety before they are even submitted to regulators for approval.
These positive results in vaccine research come after the 30th anniversary of the identification of the virus. It was an occasion that led the U.N. General Assembly (UNGA) to reaffirm its commitment to addressing the global epidemic of HIV/AIDS at a special session in New York. On the sidelines of that event, U.S. officials expressed optimism about multilateral partnerships against the disease and the prospect of finding an effective vaccine that could stop HIV contagion.
The United States is the single largest donor in the huge global effort to combat the disease. On World AIDS Day December 1, the White House released the latest statistics on the numbers of lives touched by U.S.-backed programs, including:
• 3.9 million people receiving lifesaving anti-retroviral treatment.
• 9.8 million pregnant women receiving HIV testing and counseling.
• 13 million people receiving care and support, including more than 4.1 million orphans and vulnerable children.