No One Really Knows Where The Tunnel Ends
The Murky Path Towards an HIV Vaccine
By Anabel Moore
In 1984, President Ronald Reagan’s health secretary Margaret Heckler stated that she believed a human immunodeficiency virus vaccine (HIV) would be available by 1986. In mid-January 2023, forty years after the discovery of the HIV virus, Janssen Pharmaceuticals announced the failure of yet another HIV vaccine candidate in testing.
Dubbed Mosaico, this candidate was the only HIV vaccine candidate to persist into late-stage trials. It had promised a complex defense against infection by the HIV virus, which causes acquired immunodeficiency syndrome (AIDS). Designed to contain components that targeted different subtypes of HIV worldwide, Mosaico offered optimism in the battle against the slippery, mutation-prone virus.
Yet it ultimately proved no more effective than placebo treatments. On January 13, 2023, the Johnson & Johnson company announced its termination of the Phase 3 Mosaico study, a decision which, according to experts, sets back the journey for a vaccine by three to five years.
After the runaway success and rapid implementation of mRNA COVID-19 vaccines, the idea that the scientific community could fail to conjure a vaccine with an original two-year timeline is astonishing. But HIV is different: as Richard Horton, an editor of The Lancet, noted in a 1996 New York Review of Books article, “HIV does not play by the old rules.” Not only does the virus mutate rapidly, thereby evading spike protein-specific vaccine targeting, but HIV also doesn’t replicate in any small animal model. Simian immunodeficiency virus modeling doesn’t allow for direct testing of HIV vaccines, and no human has ever cured themselves of the virus. To a greater extent, human models are ethically complex; wayward vaccines risk infecting study participants with a potentially terminal disease, despite the widespread implementation of effective (and expensive) virus suppression therapeutics.
Horton had also noted that society’s fixations on the virus, which often exceeded its focus on patients themselves, “produced some plainly absurd claims.” Even as community-based advocacy groups fought for “a face to AIDS,” in the late eighties and nineties, it seems that the conversations about HIV prevention rest in silos. There is a “face to AIDS” in needle-safety campaigns and sexual education strategies, but none in vaccine development. Vaccine development lacks a light at the end of the tunnel because no one really knows where the tunnel leads, let alone where it ends.
Interestingly, discourse about HIV cofactors’ relationship to AIDS pathophysiology still lingers. In the mid-1990s, one virologist at the University of California–Berkeley, Peter Duesberg, went as far as to claim that HIV isn’t the cause of AIDS. Instead, Duesberg argued, the crippling disease was caused by different things in different groups of individuals, blaming controlled substance use and even AZT, a drug used to treat AIDS itself. Though Duesberg was eventually discredited and cast aside by his colleagues, these early challenges emphasize HIV as an outlier amongst viral and infectious diseases.
But one thing is clear: HIV doesn’t play by any rules. Stuart Shapiro, a leader of the Vaccine Research program at the National Institute of Allergy and Infectious Diseases, wrote in 2020 that there is no incentive for the industry to develop a vaccine. According to Shapiro, “Academic scientists see an easy development path as too little a scientific challenge, or they do not even apply for funding because they fear the absence of a basic research challenge means grant applications will not be well received by peer reviewers.”
In this sense, funding for HIV vaccine research straddles the divide between being empirically driven and application-driven. Does one develop new knowledge and technologies specifically for the creation of a highly specialized vaccine? Or do they focus efforts on hijacking existing or recent technology, as was the case with the COVID mRNA vaccines, in an effort to create a product that can effectively end a global epidemic? HIV vaccine development lives in a gray space that few researchers seem keen to broach.
Regardless, the recent ending of the Mosaico trial is “a disappointment and a setback,” according to Mitchell Warren, executive director of the HIV prevention organization AVAC and quoted in a recent New York Times article. It is likely even more disappointing for the global community, particularly for regions dealing with lesser access to powerful antiretroviral medicines. While few comparisons can be made between HIV/AIDS and other viruses and diseases, it is worth mentioning that the global context of vaccine development is similar to that of other infectious complexes.
For example, the RotaShield vaccine proved highly effective against rotavirus, a disease that causes severe and life-threatening diarrhea, particularly in children. However, the vaccine was pulled from the U.S. market in 1999 following several fatal cases of the rare side effect of intussusception, wherein the intestine telescopes into itself. Policy meetings at a 2000 WHO summit in Geneva concluded the ethicality of continuing RotaShield studies in developing countries, as long as researchers gave heed to the diagnosis and treatment of intussusception; nonetheless, “without data on the vaccine’s safety and efficacy in developing countries, the U.S. rejection of RotaShield made the vaccine politically nonviable to health ministers in these nations.”
A highly effective vaccine that saved many more lives than it took was, in effect, pulled from the global market on the basis of decision-making in an affluent, relatively unaffected country. Similarly, research and development efforts toward an HIV vaccine in the United States have extreme ramifications for patients in developing countries, where the high cost of antiretroviral medication is sometimes prohibitive. The burden of vaccine development falls on wealthy, developed nations like the United States, but the burden of disease falls squarely on the shoulders of poorer, developing nations, such as those in sub-Saharan Africa.
No matter what comes next with the HIV vaccineand the future is infinitely murky — vaccine scientists, public and global health coalitions, and domestic funding agencies are in uncharted waters. HIV is one of the few vaccine efforts wherein a “warp speed” effort has been fruitless, despite massive public and private intervention on a global scale. There is much to gain, and much to lose for all parties involved — but what remains most at stake is the five hundred thousand individuals who die from AIDS each year.
Citations
Stuart Z Shapiro, “HIV Vaccine Development: 35 Years of Experimenting in the Funding of Biomedical Research,” Viruses, December 2020
Richard Horton, “Truth and Heresy About AIDS,” The New York Review of Books, May 23, 1996
Jason Schwartz, “The First Rotavirus Vaccine and the Politics of Acceptable Risk,” The Milbank Quarterly,” vol 90, №2, 2012
Apoora Mandavilli, “The Only HIV Vaccine in Advanced Trials Has Failed. What Now?” The New York Times, January 18, 2023
