Infectious disease expert Dave Wessner reports from the 24th International AIDS Conference, where researchers shared ways that Covid vaccine development might help the development of a vaccine for AIDS.
Despite nearly forty years of research, there’s still no vaccine to combat HIV/AIDS. However, recent discussions at the 24th International AIDS Conference in Montreal provided some hope that that situation might change. Roughly a year after the world first became aware of Covid-19, two vaccines that effectively reduce the risk of this disease were approved for use by the Food and Drug Administration. Lessons learned during the development of those vaccines may spur efforts to develop a vaccine against HIV/AIDS.
So why don’t we have a vaccine against HIV/AIDS?
As I’ve described before, HIV/AIDS and Covid-19 differ in myriad ways. HIV and SARS-CoV-2 are different viruses that are transmitted in different ways and cause vastly different diseases. Additionally, structural and biological differences between these two viruses have impacted our ability to develop effective vaccines.
In an overview of this issue presented at AIDS 2022, Dr. Lynn Morris of the National Institute for Communicable Diseases in South Africa delineated some of these differences. First, the HIV genome becomes integrated into our DNA. As a result, its genetic material, the blueprint for creating new virus particles, remains embedded within our cells, shielded from our immune system.
Second, HIV mutates at a very high rate. Despite the current concerns about SARS-CoV-2 variants, the genome of this virus is fairly stable. HIV, in contrast, exhibits a much higher mutation rate. As a result, HIV exhibits more structural diversity, thereby thwarting our immune response. Third, the envelope protein of HIV, functionally equivalent to the spike protein of SARS-CoV-2, has a complex shape and is heavily glycosylated, or coated with sugars. Both of these properties mask HIV from an effective immune response.
Finally, and maybe most significantly, broadly neutralizing antibodies, or bnAbs, seem to develop only in a minority of people infected with HIV and then only years after the initial infection. This hinders one of the primary means through which vaccines work.
What are broadly neutralizing antibodies?
Quite simply, broadly neutralizing antibodies are proteins produced by our immune system that can effectively block infection by genetically and structurally diverse variants of a virus. Such antibodies should be effective weapons against viral infections. However, natural infections with HIV do not generally result in their formation. Vaccination strategies explored over the past few have also been unsuccessful at stimulating their development. The result? Our immune system does not clear the virus after a natural infection and the potential vaccines examined so far do not effectively block new infections.
In a 2019 article in Science, Dr. Barton Haynes of the Human Vaccine Institute at Duke University and his colleagues described a strategy for circumventing this problem. They noted that the rare bnAbs targeting HIV that have been characterized contain a series of “improbable mutations” that presumably arose during the maturation of the immune cells producing them. The trick, then, may be to use a prime-boost vaccination strategy in which the primary vaccine causes the immune system to produce bnAb precursors and the secondary vaccine then activates those rare cells that have accumulated the mutations needed to make effective, mature bnAbs. The idea seems straight-forward. However, the properties of effective secondary vaccines have not been determined.
What can be learned for HIV vaccines from the development of Covid vaccines?
As Dr. Haynes noted at AIDS 2022, traditional vaccine development approaches, which generally use proteins to stimulate the immune system, are slow and costly. The Moderna and Pfizer-BioNTech Covid-19 vaccines, however, make use of a mRNA platform. This approach has several benefits over more traditional vaccine development processes. Most notably, it is cheaper and faster. In theory, many slightly different vaccines could be developed and tested relatively quickly. Researchers hope that this flexibility will allow them to rapidly screen many potential secondary vaccines. Hopefully, one of them will induce the long sought after broadly neutralizing antibodies.
The search for an effective HIV vaccine has been a slow, arduous process. But the 40-year struggle has benefited the vaccine field in many ways. We understand the human immune system better because of the work done on HIV. Arguably, the Covid-19 vaccines were developed so rapidly in part because of lessons learned from HIV. Now, perhaps, lessons learned from Covid-19 will impact the development of an HIV vaccine.
