For the first time, researchers say infusions of antibodies can prevent HIV infection
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Researchers demonstrated for the first time that infusions of antibodies can prevent HIV infection.
According to clinical trial results presented at the HIV Research for Prevention virtual meeting, infusions of a broadly neutralizing antibody (bNAb) called VRC01 were effective at preventing infection from HIV strains that were sensitive to the antibody, although the infusions offered no protection against unsusceptible strains.
“The trial, as a test of concept, was wonderfully successful and sets the landmark that we can use broadly neutralizing antibodies for the prevention of HIV,” Lawrence Corey, MD, president and director emeritus of the Fred Hutchinson Cancer Research Center, said during a press briefing.
“This will be a new modality and a new toolbox, and it opens up the field for the development of antibody cocktails and monoclonal antibodies,” said Corey, who is protocol chair of the Antibody-Mediated Prevention (AMP) studies and the principal investigator of the HIV Vaccine Trials Network (HVTN).
75% effective
In one study, Corey and colleagues enrolled around 2,700 transgender people and cisgender men who have sex with men in Brazil, Peru, Switzerland and the United States. Another study enrolled more than 1,900 HIV-negative cisgender women in seven African countries — Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. Participants received an IV infusion of VRC01 every 8 weeks for 80 weeks at a dose of either 10 mg/kg or 30 mg/kg, or a placebo. They were assessed for HIV acquisition in 4-week intervals.
VRC01 was calculated to be 75% effective at preventing HIV infection from isolates sensitive to the antibody. However, because only 30% of isolates were sensitive to the antibody, protection from VRC01 was not statistically significant overall compared with placebo, the researchers reported.
Nyaradzo M. Mgodi, MBChB, MMed, a researcher on the VRC01 trials, told journalists in a preconference webinar that they set out to answer four questions: “Is VRC01 safe to give to people? Are people able to tolerate the antibody without becoming too uncomfortable? Does the antibody lower people’s chances of getting HIV? And if it does, what is the optimal dose?”
Mgodi said there are no plans to seek licensure for VRC01. Instead, the proof of concept study will be used to design future studies to evaluate antibodies and combinations of antibodies to prevent HIV.
Corey noted that the cost of antibodies is gradually dropping and that bNAb treatment could be economically feasible in the future.
“HIV is always a formidable pathogen — what you hope happens doesn't always necessarily happen,” he said. “We're not disappointed in this study because we got what we really wanted — to have a marker of success that leads the field forward and showed that we could demonstrate the proof of concept.”
‘Foundation’ for future research
In a statement, National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, said the findings “establish the concept that passive administration of a broadly neutralizing antibody can prevent acquisition of susceptible HIV strains.”
“Insights gleaned from the AMP studies lay the foundation for future development of long-acting antibody-based HIV prevention tools and, ultimately, a vaccine,” Fauci said.
As noted on the trial’s website, giving people infusions of antibodies skips the step of vaccinating them and directly gives them the antibodies they might produce after vaccination.
Scientists have long sought a vaccine against HIV.
According to Pontiano Kaleebu, MD, PhD, who heads the Uganda Virus Research Institute, more than 250 HIV vaccine trials have reached phase 1 or 2 development since 1987, and 10 have reached phase 2b or phase 3. Kaleebu recorded a presentation on the subject for journalists covering the conference.
Early last year, Fauci’s NIAID stopped a phase 2b/3 trial, HVTN 702, after an independent data and safety monitoring board found that the vaccine was not working — a result that generated a lot of disappointment in the scientific community.
The trial had enrolled more than 5,400 participants at 14 sites in South Africa to test a vaccine based on a regimen that was found to be around 31% effective during a vaccine trial in Thailand, according to results released in 2009.
The cancellation left three ongoing HIV vaccine efficacy trials, including the phase 2b HVTN 705 trial, nicknamed Imbokodo, which is being conducted in five southern African countries; and the phase 3 HVTN 706 trial, called Mosaico, which is taking place in eight North American, South American and European countries, including the U.S. Both are evaluating investigational vaccines that use “mosaic” immunogens designed to provide maximum coverage against circulating HIV strains, Kaleebu said.
There also is a lot of interest in using messenger RNA vaccine technology — the same technology used in the two authorized COVID-19 vaccines in the U.S. — for HIV and other infections, including malaria and tuberculosis, according to Fauci.
Moderna, which developed one of the COVID-19 vaccines, has already expanded its mRNA program to develop vaccines against HIV, influenza and Nipah virus.
“HIV research absolutely helped COVID-19. Now that we have a successful vaccine with mRNA, it’s going to go back,” Fauci told journalists ahead of the conference. “Everything that goes around comes around. We’re going to hopefully get more insight into HIV vaccines.”
References:
Mkhize NN, et al. Abstract 1188. Presented at: HIV Research for Prevention; Jan. 27-28 and Feb. 3-4, 2021 (virtual meeting).
Perspective
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Broadly neutralizing antibodies, which arise naturally in some people living with HIV, could have a role in HIV prevention or treatment. This study from the HIV Vaccine and Prevention Trial Networks (HTN 704/HPTN 085) was a proof of concept study to determine if a bNAb named VRC01 (targeting the CD4 binding site of HIV-1) decreased HIV acquisition among men and transgender persons who have sex with men (MSM/TG) and women. Study participants were randomly assigned to receive 10 IV infusions over 80 weeks of VRC01 at two dosing regimens or placebo. Moreover, sensitivity of the HIV strains to the bNAb was determined by a test that measures viral susceptibility to neutralization. Overall, VRC01 was 75% effective at preventing acquisition of sensitive HIV strains across the 80-week study period in both women in sub-Saharan Africa and MSM/TG in the Americas and Europe. The key determinant of how well the antibody worked to prevent HIV was whether the HIV strain to which a person was exposed was susceptible; indeed, VRC01 did not prevent acquisition of resistant HIV strains.
This study is relevant in that it suggests that bNAbs will be effective as another tool in HIV prevention, although a combination of bNAbs may be required to offer effective protection against a wide variety of HIV strains. This study also has relevance for HIV vaccines, which would be designed to stimulate such antibodies. Therefore, this is a very exciting proof of concept study for the role of bNAbs in HIV prevention.
Perspective
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We’ve known for years that circulating antibodies play a role in HIV control. While not the easy “home run” we may once have believed, this report provides extremely important insight into their potential role in preventing HIV acquisition. We know that HIV mutates in response to immunologic pressure as well as to the presence of less potent antiretroviral drugs. This trial employed an antibody chosen for its ability to neutralize a rather broad array of HIV isolates and infused this in individuals at risk of becoming HIV-infected and followed participants to see how many acquired HIV infection. The investigators report that the antibody infusions were very effective (about 75%) if the HIV to which they were exposed was sensitive to the antibody in the study. The treatment, however, did not prevent infection from HIV variants that were less sensitive to this antibody. While this approach is unlikely to find a common role in population-level HIV prevention strategies, it will still be very valuable to better design newer efforts to employ antibodies or combinations with broader neutralization and potentially exploring these as therapeutic agents in attempts to cure HIV infection. It’s great to see in HIV as well as in COVID-19 applications of antibodies in treatment and prevention.
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Corey L, et al. Abstract 1480. Presented at: HIV Research for Prevention; Jan. 27-28 and Feb. 3-4, 2021 (virtual meeting).
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