National HIV Vaccine Awareness Day is observed annually on May 18 to mark the progress made in developing an effective HIV vaccine, to acknowledge those who have contributed to vaccine research and to educate communities about the importance of this research.
“The road to finding a vaccine for HIV has certainly been a long and arduous one,” Rowena Johnston, PhD, vice president and director of research at amfAR, the Foundation for AIDS Research, told Infectious Disease News. “It began in the earliest days of HIV research in the 1980s as soon as they discovered the cause of AIDS as HIV. Some people thought that at least having identified the virus would help in terms of developing a vaccine. It turns out that HIV is so exquisitely adapted for the human body that so many of the things we try against the virus just don’t work.”
Johnston said there are countless ways HIV can “hide” in the body, making it difficult for the immune system to attack the virus. Moreover, the virus can mutate rapidly, further complicating vaccine development. While exploring the use of a live-attenuated HIV vaccine is too dangerous since the virus may mutate into a stronger version, an inactivated virus is not strong enough to stimulate the immune system, she said. This has forced researchers to explore unprecedented ways to develop both a preventive and a therapeutic vaccine.
“We’re taking this view that what has traditionally worked in vaccines clearly isn’t going to work for HIV, so let’s see if we can take a look at a broader range of approaches and take advantage of what we’ve learned from all those people who have come before us in vaccine research,” Johnston said. “When people think of vaccines, they normally think of them as a way in which you would prevent an infection from happening. It is becoming clear that a vaccine could be very useful in trying to cure somebody.”
Researchers study vaccine use in “shock-and-kill” strategy
Researchers at amfAR’s Institute for HIV Cure Research currently are focused on the “shock-and-kill” strategy, which explores the use of vaccines and drugs, particularly toll-like receptor (TLR) agonists, in curing HIV.
In patients with HIV, a small fraction of immune cells remains infected with a latent virus, even with the use of ART, according to Johnston. Since the immune system is unable to detect and, therefore, fight against this latent reservoir, researchers are investigating whether TLR agonists can be used to provoke the virus to replicate and enhance the immune system’s ability to kill the cells producing the virus, possibly with the help of a vaccine.
“TLR agonists actually stimulate various arms of the immune system,” Johnston said. “Then, once the immune system notices what it’s supposed to fight against, it’s better equipped to do so.”
Studies assess efficacy of preventive vaccines
Meanwhile, a strategy in developing a preventive HIV vaccine involves the role of broadly neutralizing antibodies (bNAbs) in blocking HIV strains from infecting cells. Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in a statement that a small proportion of infected patients can naturally develop bNAbs 2 or more years after infection, which is too late to significantly benefit the patient. Researchers are identifying and engineering numerous bNAbs, however, and testing their ability to determine whether vaccines that elicit similar antibodies can prevent infection, he said.
Anthony S. Fauci
Today, Fauci also announced the launch of a new phase 2b/3 trial — scheduled to begin in November — that will study the efficacy of a preventive vaccine candidate in South Africa.
“For the first time in 7 years, the scientific community is embarking on a large-scale clinical trial of an HIV vaccine, the product of years of study and experimentation,” Fauci said in a press release. “A safe and effective HIV vaccine could help bring about a durable end to the HIV/AIDS pandemic and is particularly needed in southern Africa, where HIV is more pervasive than anywhere else in the world.”
The HVTN 702 study will test an investigational vaccine that demonstrated modest efficacy in the RV144 trial in Thailand. During the RV144 trial, the vaccine was 60% effective at preventing HIV infection 1 year after vaccination, and 31.2% effective 3.5 years after vaccination.
The decision to launch the trial is based on early data from the HVTN 100 phase 1/2 trial, which demonstrated an improved version of the vaccine used in RV144 is safe and produces a robust immune response.
“We’re all aware that HIV is, in recent times, probably the most devastating epidemic that mankind is facing,” Johnston said. “The solution to HIV is going to come from both [prevention and cure]. Interestingly, vaccines might be a key part of the answer to both ends of that spectrum. Vaccines clearly are going to play a role in us being able to prevent HIV infection, and surprisingly, vaccines might be a really good part of the answer to curing HIV infection, as well.”
To mark the occasion of HIV Vaccine Awareness Day, Infectious Disease News has compiled a list of stories covering research in vaccine development.
TSRI scientists capture detailed picture of HIV structure
Researchers from The Scripps Research Institute have captured a high-resolution image of an almost fully intact HIV protein responsible for infecting host cells. The image revealed potentially vulnerable targets for broadly neutralizing antibodies, which may help guide vaccine development.
“This structure has been elusive because its fragility typically causes it to fall apart before it can be imaged,” Andrew Ward, PhD, associate professor at TSRI, said in a press release. “Now that we know what the native state looks like, the next step is to look at vaccine applications.” Read more.
Researchers explore new HIV vaccine target
A research team, led by the NIH, discovered a vulnerable site on HIV that may be used as a target for future vaccines and identified a broadly neutralizing antibody that binds to the site, according to recent findings.
The target site, called the fusion peptide, is a string of eight amino acids that allows the virus to fuse and infect a cell, and has a simpler structure compared with other vulnerable sites studied for HIV vaccine development. Read more.
Separate, coadministration of investigational HIV, HCV vaccines induce similar responses
Phase 1 data presented at the International Liver Congress in Barcelona, Spain, showed that investigational HIV and hepatitis C virus vaccines administered simultaneously in a prime-boost regimen were well-tolerated and induced similar immune responses compared with individual vaccine administration.
“Finding effective vaccinations against the world’s biggest killers is a huge and pressing problem,” Laurent Castera, MD, PhD, European Association for the Study of the Liver secretary-general, said in a press release. “This study shows for the first time that it is possible to generate simultaneous immune response against diseases HCV and HIV, raising the possibility of a combined vaccination.” Read more.
VIDEO: HIV prevention strategies focus on vaccine development
Myron S. Cohen, MD, chief of the division of infectious diseases and director of the Institute for Global Health and Infectious Diseases at the University of North Carolina, provides an overview of behavioral and biological strategies for HIV prevention that were discussed at IDWeek 2015.
The meeting largely focused on vaccine development and the role of broad-neutralizing antibodies, which are generated by 10% of individuals with HIV and kill between 80% and 90% of HIV viral strains, Cohen said. The potential of broad-neutralizing antibodies for vaccine development will be assessed in a passive immunity study called HVTN 703/HPTN 081, or the AMP study. Watch the video.
Researchers investigate early stages of HIV-neutralizing antibody
Scientists at The Scripps Research Institute and collaborating institutions have identified and characterized an immature, or “teenage,” antibody with broadly neutralizing signatures isolated from an elite controller. The researchers said their findings, published in Immunity, may be useful for future HIV vaccine development.
“This is actually the first example of how we can go back to the really early stage to see how this particular antibody lineage was born and can develop,” TSRI researcher and biologist Jiang Zhu, PhD, said in a press release. Read more.
– by Stephanie Viguers.
Disclosures: Fauci and Johnston report no relevant financial disclosures.