Scientists are reporting encouraging advancements in HIV vaccine research, identifying new pathways that could eventually lead to an effective inoculation against the virus that causes AIDS. While a commercially available vaccine still remains years away, the latest findings suggest researchers are making step-by-step progress, overcoming past roadblocks through innovative techniques.
Novel Antibodies Show Ability to Neutralize Diverse HIV Strains
In a new study published this month in Science Translational Medicine, National Institutes of Health (NIH) scientists detail the discovery of two new potent antibodies that show an exceptional capacity to neutralize different variants of HIV across multiple strains.
Dubbed 21AT06 and 21AT07, both antibodies were isolated from a participant enrolled in the International AIDS Vaccine Initiative (IAVI) Protocol C program in Africa which studies people showing signs of strong immunity against HIV. What makes the antibodies distinct is that rather than targeting the spike on the virus surface like most, they bind uniquely to sugars on HIV’s outer envelope, providing a defense that the virus finds difficult to evade through mutation.
“The 21AT06 and 21AT07 antibodies neutralize HIV isolates from all major strains tested,” explained Dr. Peter D. Kwong, Chief of the Structural Biology Section at the NIH’s National Institute of Allergy and Infectious Diseases and the study’s senior author. “This is an encouraging discovery that provides an important guide in our development of a global HIV vaccine able to protect against a majority of circulating strains of the virus.”
In laboratory cultures of immune cells and humanized mouse models, both antibodies showed potency in neutralizing a variety of HIV viral isolates, including 16 transmitted founder variants that play an instrumental role in establishing infection. Such comprehensive activity against an array of strains has rarely been observed in other HIV antibodies to date.
While clinical studies will be required to evaluate safety and pharmacokinetics, the antibodies’ exceptional breadth and potency make them promising preventative and therapeutic candidates, either directly administered alone or through vaccination.
Vaccine Concept Shows 97% Protection Rate Against SHIV in Monkeys
Separately, NIH scientists announced this month that an experimental HIV vaccine concept they developed was able to provide 97% protection against an HIV-like virus called simian-human immunodeficiency virus (SHIV) in rhesus macaque monkeys. Described in a study published in Nature Communications, it represents the first vaccine concept to achieve such a high rate of success in these primates.
The vaccine prototype utilises the newly discovered anti-HIV antibodies 21AT06 and 21AT07 referenced above to try to train the body to produce them on its own to block HIV infection. Researchers engineered harmless virus-like particles containing components of HIV and the two antibodies, exposing them to rhesus macaques to trigger an immune response. They then administered different variants of SHIV to test the vaccine’s effectiveness.
In 17 out of 18 monkeys given the vaccine then infused with SHIV, they recorded high levels of the antibodies in the blood which protected them against multiple strains. All control animals given placebos became infected.
“To date this is the most effective vaccination strategy that we’ve tested in monkeys,” said Dr. Richard Schwartz, Assistant Clinical Investigator at the NIH’s National Institute of Allergy and Infectious Diseases. “We’re now focused on optimizing the vaccine prototype and beginning clinical trials to determine if this vaccine concept can safely provoke the types of antibody responses needed to protect people.”
While protection was not absolute, the results provide a proof of concept that using specifically designed anti-HIV antibodies as part of vaccination could train broadly neutralizing antibodies that target the virus’s weak spots. This opens up a promising avenue scientists can continue refining to inch towards a safe and effective inoculation.
mRNA Vaccines Show Ability to Elicit Difficult-to-Induce Antibodies
mRNA vaccine technology has accelerated rapidly following the success of Pfizer/BioNTech and Moderna’s COVID-19 shots. Now scientists at Duke University are harnessing mRNA to tackle HIV, using it to spark the production of rare antibodies needed to combat infection. Their approach centers on training B cells rather than other immune cells often targeted in past attempts.
As described in a new study published in Science Immunology, the researchers used banks of B cells isolated from an HIV-infected individual endowed with broadly neutralizing antibodies. Through mRNA imprinting and activation, they rewired these mature cells to generate three types of antibodies against the CD4 binding site, a key target for blocking viral entry.
These difficult-to-induce antibodies would arise in only 10-30% of people even after years of natural HIV infection. But the mRNA vaccinations elicited them reliably in test animals, even when using B cells not pre-selected for responsiveness.
“We found a way to consistently induce what were previously very rare antibodies,” summarized Dr. Barton Haynes, senior author of the study. “We solved a major problem plaguing HIV vaccine research in that very few people make these antibodies and we don’t know why.”
The researchers noted that while more refinement is needed, the experiments demonstrate how mRNA technology could side step past obstacles in training broadly neutralizing antibodies against HIV. Their customizable nature also allows for updating viral specifics when new variants emerge.
“This provides a potential pathway toward solving part of the puzzle of how you can design a vaccine that elicits broadly neutralizing antibodies against HIV – which many people consider the holy grail of HIV vaccine research,” Haynes said.
‘Priming and Polishing’ Approach Shows Promise
As these cutting-edge findings highlight, after decades of frustrations, HIV vaccine research is gaining momentum again thanks to breakthrough approaches on multiple fronts. Scientists emphasize it still remains a complex challenge requiring continued coordination. To aid these efforts, the Global HIV Vaccine Enterprise – an alliance of stakeholders working towards developing, testing, licensing and deploying vaccines accessible globally – held a summit this month taking stock of progress.
In their published review of current roadblocks and innovations discussed at the summit, researchers outlined a stepped “priming and polishing” strategy gaining traction.
The idea combines using one type of vaccination to stimulate initial B cell response and priming towards useful antibody production, then following on with a second modality to “polish” the antibodies over time into broadly neutralizing forms. This could sidestep the immense challenge of trying to directly elicit these antibodies in one shot.
They detail the summit’s examination of different prime-polish approaches, from viral vectored vaccines to mRNA boosters, that evidence suggests can reliably prime development of antibody lineages on the right evolutionary paths. Refining delivery mechanisms and immunization schedules will be key next steps.
“After decades of research, the field has made substantial advances, providing optimism that development of an effective HIV vaccine is feasible using stepwise prime and polish approaches,” the review states. It underscores that rather than compete, integrating promising techniques already in progress could accelerate solutions. Continued collaboration and resource sharing remains vital.
While major hurdles persist, the latest HIV antibody and vaccine research clearly signals promising inroads towards protection against the disease that has claimed over 40 million lives since 1981. Multiple innovative approaches are demonstrating an ability to stimulate and produce difficult-to-obtain antibodies while evading previous dead ends.
“Progress is incremental,” said Dr. Anthony Fauci, top infectious disease expert heading the U.S.’s pandemic response. “But each increment represents additional momentum towards ultimately getting a safe and effective HIV vaccine that will have a substantial impact on the trajectory of the pandemic that has gone on now for more than 40 years.”
Global health leaders caution that alongside scientific breakthroughs, equitable vaccine access will remain a central issue needing proactive policy planning as concepts advance towards testing and viability.
But the tails winds now emerging across HIV vaccine development fronts after years of limited progress are fueling optimism within the field.
“We’re not there yet,” Fauci affirmed. “But we’re getting closer.”
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