HIV/AIDS at 40: Progress has been plentiful, but vaccine still elusive

June 4 (UPI) -- Forty years ago, the AIDS epidemic arrived when the first cases were officially reported by the Centers for Disease Control and Prevention. But while there has been monumental progress fighting the virus since then, questions remain about why there still is no HIV vaccine.

The development of a COVID-19 vaccine, in record time last year, has intensified questioning why an HIV vaccine remains elusive.

COVID-19 has killed millions, but even a pandemic of that magnitude still doesn't compare to the catastrophic death toll that's been attributed to AIDS over the past four decades -- an unrelenting disease caused by a virus that effectively wipes out the body's immune system.

While both diseases are lethal, a stark difference in their mortality rates exists. Untreated, AIDS is a death sentence almost 100% of the time. Forty years of study have given scientists great depth of knowledge about an affliction that doctors initially found in homosexuals and some observers called the "gay cancer."

The dawn of HIV/AIDS

Researchers believe the HIV virus originated a century ago, when it jumped from animals to humans around the 1920s. It then took about 60 years for it to begin to spread among humans.

In its Morbidity and Mortality Weekly Report on June 5, 1981, the CDC officially brought the disease to the fore by describing the first cases in Los Angeles found in five previously healthy young men. It wasn't long before more cases were seen in New York City, San Francisco and other U.S. cities.

The report noted that two of those first five patients had died and two acknowledged having frequent homosexual contact with various partners.

"The fact that these patients were all homosexuals suggests an association between some aspect of a homosexual lifestyle or disease acquired through sexual contact," the CDC's MMWR said, although it took scientists a long time before they were able to prove that AIDS could be transmitted sexually.

By the end of 1981, more than 100 gay men were dead of the disease, and a stigma enveloped the virus as terms like "gay plague" were widely used. Panic grew further when some insisted that it could be contracted just by being near an infected person.

"An increasing number of men, mostly homosexuals, are suffering from a mysterious new syndrome that turns usually harmless viruses and bacteria into killers," UPI reported in December 1981.

"It's an extraordinary business and really quite frightening because nobody knows the cause," Dr. Frederick Siegal, an immunologist at Mount Sinai Medical Center in New York City, told UPI at the time.

"I wouldn't be surprised if it's something we've never heard of before."

Four decades, and no vaccine

Beginning with advances in medications in the 1990s, people with HIV can now expect to live a long life if they begin treatment early. Also, scientists learned a few years ago that the treatments also prevent infected people from transmitting the disease to others.

But after billions of dollars spent on research, the world is still waiting for a vaccine. Though the cocktail of drugs make HIV a manageable disease, they don't amount to a cure.

Dr. Ronald C. Desrosiers, a professor of pathology at the University of Miami Miller School of Medicine, said the complexity of HIV is the reason a vaccine has been elusive.

"The problem is not a failure of government. The problem is not lack of spending. The difficulty lies in the HIV virus itself. In particular, this includes the remarkable HIV strain diversity and the immune evasion strategies of the virus," he wrote in The Conversation in May.

Desrosiers, whose lab discovered the monkey version of HIV, says the virus' continuous replication means it needs a vaccine with an "absolute sterilizing barrier" to block the copying process. Other traditional vaccines, by contrast, need only to keep a virus from reproducing.

While researchers could produce a vaccine to spur antibodies for one particular strain, it wouldn't be effective against the thousands of strains that HIV could produce. Also, Desrosiers said, HIV has evolved over time to protect itself.

For comparison, HIV and the coronavirus both have a spiked protein on their surfaces, but Desrosiers says the HIV virus is better protected from antibodies because it has a heavier glycoprotein.

In an email to UPI, he said that his research could ultimately find a way to better combat HIV.

"I am optimistic about one thing, a thing that I am devoting my life to -- long-term delivery of potent broadly neutralizing antibodies using an AAV (adeno-associated virus) vector," he wrote.

"It is not a vaccine in the classic sense, but it is analogous in that it is directed to preventing infection, or curing infection."

Today, HIV-infected patients can take medications to mute the virus to undetectable levels. But the disease would return to full force once the medications are stopped -- thus, highlighting the need still for a cure.

COVID vaccine to HIV vaccine?

Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said the COVID-19 vaccine would not have arrived so quickly in 2020 without the years and years of efforts searching for a HIV vaccine.

Warren said the past few decades of research to understand human immune responses have helped speed up the process. He said messenger RNA (mRNA) development from HIV vaccine studies were effectively repurposed to make some of the COVID-19 vaccines. Both Pfizer and Moderna use mRNA in their shots.

Genetically engineered mRNA tells the body's cells how to make the S protein found on the surface of the COVID-19 virus so that antibodies can fight it. A similar process could ultimately be found to target HIV.

"Simply put, the world is better positioned today than ever before to develop an HIV vaccine -- if the HIV research effort can build on the COVID experience the way that COVID built on HIV," Warren wrote in an April guest column in Science Speaks.

"The cutting-edge mRNA technology used in several successful COVID vaccines, for example, holds great promise for HIV vaccine research. [Recently,] the U.S. National Institutes of Health and Moderna scientists presented initial data that an mRNA vaccine protected monkeys against HIV-like virus."

Warren also said it's likely that coordinated global efforts that fast-tracked COVID-19 vaccine development would also be needed to complete an HIV vaccine.

There has been some progress in the vaccine arena over the past four decades.

A vaccine candidate in Thailand in 2009 proved somewhat protective against HIV, but not enough for wide-scale production. At the time, its clinical trial of 16,000 volunteers made it the largest HIV vaccine trial in history.

Two other large studies are currently testing an adenovirus-based vaccine, followed by a booster that contains proteins from multiple HIV strains. Other vaccines have previously used adenoviruses, which are modified virus vectors that can deliver DNA coding for certain antigens.

William Schief, a professor and immunologist at the Scripps Research Institute in La Jolla, Calif., said the search has posed a major challenge because the virus has evolved so much over the last 40 years.

"It's really like 50 million different viruses around the world right now," he said in a video posted online in February, noting that the protein on the HIV virus is more "devious" than the one that causes COVID-19.

Schief and collaborators at Scripps and the International AIDS Vaccine Initiative have been working toward an HIV vaccine for more than a decade using a technique called germline targeting, which is designed to activate rare naive B cells. The cells produce broadly neutralizing antibodies that could target weak spots on the HIV virus' outer surface.

They said the vaccine candidate activated B cells in 97% of volunteers during a Phase 1 trial and caused no adverse effects.

"The results were surprisingly strong," Schief said.

Several additional trials are still needed, though, to gauge the vaccine's potential.

Scripps and IAVI are also working with Moderna on a different mRNA vaccine, which if successful could accelerate the arrival of an HIV vaccine.

"We have not solved the problem yet," Schief says in the video. "This is the first step."