Where’s the HIV Vaccine?
National HIV Vaccine Awareness Day is May 18. Photo illustration by Shutterstock
Billions of dollars are spent on HIV vaccine research. Many scientists have devoted their careers to the effort. But it hasn’t been enough: Dozens of HIV vaccine candidates have shown promise, only to fail in large clinical trials.
Editor’s Note: To mark this year’s National HIV Vaccine Awareness Day (May 18) palabra. is publishing this important reminder of the work yet to be done on the elusive HIV vaccine. The story was produced with the support of the NLGJA: The Association of LGBTQ Journalists and the Let's Stop HIV Together campaign, in collaboration with the Partnering and Communicating Together protect of the U.S. Centers for Disease Control and Prevention.
This year's HIV Vaccine Awareness Day on May 18 comes at a time when vaccines are getting unprecedented attention worldwide. Three highly effective COVID-19 vaccines were developed and authorized in the United States in under a year.
This has led many to wonder why, after nearly 40 years of research, we still don't have a vaccine for HIV.
Despite amazing advances in HIV treatment and prevention—including a daily prevention pill (pre-exposure prophylaxis, or PrEP)—HIV vaccines are still a pressing need.
Approximately 38,000 people a year are newly diagnosed with HIV, and disadvantaged communities are particularly vulnerable. In 2018, Latinos made up 27% of new HIV diagnoses and African Americans accounted for 42%—both well above their representation in the general U.S. population. Two-thirds of people newly diagnosed with HIV are gay and bisexual men, and transgender people are also disproportionately affected. Young people account for one in five new cases, but they are least likely to be aware they have HIV.
While PrEP use has increased dramatically since its approval in 2012, it still is not reaching far enough into some communities. The continuing high number of new infections shows the need for better prevention methods—and some experts think vaccines are the only way to get to zero.
Illustration courtesy of Shutterstock.
The Challenges of HIV Vaccines
Why have HIV vaccines been so hard to develop—and could advances that led to the COVID-19 vaccines help move that effort along faster?
Although the early response to AIDS was painfully slow, today the federal government, nonprofits, and pharmaceutical companies spend billions of dollars on HIV vaccine research, and many scientists have devoted their careers to the effort. But all that money and brainpower haven't been enough. While dozens of HIV vaccine candidates have shown promise in laboratory and animal studies, so far they have all failed in large clinical trials.
There are several reasons why it’s harder to develop vaccines for HIV than for SARS-CoV-2, the new coronavirus that causes COVID-19. While most people develop natural immunity against the coronavirus, only a small subset produce a robust immune response against HIV.
HIV mutates frequently as it replicates, producing countless variants. Most people with HIV do produce antibodies against the virus, but these usually don’t recognize the wide variety of strains. Plus, HIV's outer envelope is covered with sugar molecules that hide it from the immune system.
"A vaccine generally mimics the body’s natural immune reaction to a virus, which usually results in it being cleared," said Dr. Anthony Fouci, director of the National Institute of Allergy and Infectious Diseases, at a recent HIV prevention conference. "But with HIV, it doesn’t. So a vaccine has to elicit an immune response that’s better than nature—and that’s hard to do."
Medical science is racing toward an HIV vaccine, a drive that’s proven difficult. Photo by Shutterstock.
Researchers have tried numerous approaches in the quest for an HIV vaccine. Simply showing the immune system viral proteins or a weakened version of the whole virus does not work for HIV, as it does for SAR-CoV-2 and many other viruses. More sophisticated strategies are required. An effective HIV vaccine would likely need to produce so-called broadly neutralizing antibodies that recognize different strains of the virus. Ideally, a vaccine would stimulate both antibody production and T-cell responses.
The first vaccine (AIDSVAX) tested in large Phase 3 trials in the early 2000s used engineered versions of envelope proteins from different HIV strains; unfortunately, it was unsuccessful. Another attempt used an inactivated adenovirus (a common cold virus) to deliver three internal HIV proteins. Although the vaccine triggered HIV-specific responses in early studies, a larger trial, which enrolled more than 3,000 volunteers, was halted ahead of schedule after it failed to reduce the risk of HIV infection.
The only hint of success came from one trial in Thailand, which tested AIDSVAX plus another vaccine (ALVAC) that delivers DNA for HIV proteins using a canarypox virus vector. In 2009, researchers reported that this combination reduced new HIV infections by 31%. But a larger trial known as Uhambo, which enrolled more than 5,000 people in South Africa, also stopped early in February 2020 because infection rates were similar in the vaccine and placebo groups.
There are now just two large HIV vaccine trials underway. Both are testing a primer vaccine that uses an adenovirus type 26 vector similar to the one used for the Johnson & Johnson COVID-19 vaccine. Early studies showed that this vaccine plus various boosters induced strong antibody and T-cell responses and protected monkeys exposed to an HIV-like virus.
"Advances in HIV vaccine science have literally paved the way for SARS-CoV-2 vaccines. What goes around comes around … I expect this to feed back into HIV vaccine development."
-Dr. Anthony Fauci
The Imbokodo trial, started in 2017, has recruited more than 2,600 young women in southern Africa. The Mosaico study, aims to recruit 3,800 gay and bisexual men and transgender people in North America, South America, and Europe. Results are expected in 2022 and 2024, respectively.
Further back in the pipeline, researchers are exploring new ways to make HIV vaccines more effective. These include alternative viral vectors and engineered versions of HIV proteins that are more easily recognized by the body’s specialized immune cells that produce broadly neutralizing antibodies. One approach, known as germline targeting, uses a series of vaccines to spur production of these rare immune cells and train them to make effective antibodies.
The messenger RNA (mRNA) technology used for the highly effective Moderna and Pfizer-BioNTech COVID-19 vaccines is also being explored for HIV. This approach uses lipid nanoparticles, or fat bubbles, to deliver genetic blueprints for making viral proteins, in effect turning cells into production factories. Moderna, BioNTech, and other companies are working on mRNA HIV vaccines.
For example, scientists are testing combinations of mRNA vaccines that contain blueprints for envelope proteins from three types of HIV found in different regions of the world. Researchers from the National Institutes of Health recently reported that a multi-shot vaccine regimen triggered production of neutralizing antibodies in monkeys. Some monkeys exposed to an HIV-like virus did not become infected, and infection was delayed in others. Another approach uses mRNA to deliver blueprints that instruct other types of cells—besides the usual specialized B cells—to build broadly neutralizing antibodies.
How You Can Help Vaccine Research
The success of the COVID-19 vaccines shows how basic science can lead to unexpected breakthroughs. While they may appear to have come out of nowhere, these vaccines build on decades of research—much of it done by scientists working on HIV.
"Advances in HIV vaccine science have literally paved the way for SARS-CoV-2 vaccines," according to Fauci. "What goes around comes around, and I expect this to feed back into HIV vaccine development."
But progress in vaccine research depends on volunteers willing to roll up their sleeves and take part in clinical trials. Participating in a trial is safe, as experimental vaccines are extensively tested in laboratory and animal studies before they are given to people. Because it would be unethical to deny at-risk participants proven prevention tools, trials provide condoms and risk-reduction counseling and some offer PrEP.
To ensure that new HIV vaccines will work for everyone, it's crucial that clinical trials include a diverse range of participants that reflect the global epidemic. To date, much HIV basic research has been weighted toward white gay men, so researchers are eager to enroll more women and people of color.
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To learn more about participating in vaccine research and to find out about open studies, visit the HIV Vaccine Trials Network (https://www.hvtn.org/en.html).
To find resources about HIV treatment, prevention, and testing, visit the CDC’s Let’s Stop HIV Together Campaign page https://www.cdc.gov/stophivtogether/.
#HVAD #HVAD2021 #StopHIVTogether #EndHIVEpidemic
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Liz Highleyman is a health journalist who has covered HIV for more than 20 years, after participating in AIDS activism with ACT UP/Boston. She is the science editor for POZ magazine, and she’s written for publications including aidsmap, The Body, and the Bay Area Reporter. She studied public health at Harvard T.H. Chan School of Public Health. Highleyman lives in San Francisco with her partner and two beagles.