Few viruses have aroused as much fear as HIV. Although it was discovered almost 40 years ago, we still do not have a vaccine or a cure. But the COVID-19 pandemic has rivaled that level of fear as researchers rush to find a vaccine for SARS-CoV-2, the virus that causes the disease. The biggest question to ask yourself: will developing a vaccine prove to be just as upsetting?

The answer to this question remains to be seen, but there may be a lot we can learn from comparing the two viruses. However, when we think about vaccine development, it’s important to remember that HIV and SARS-CoV-2 are very different viruses. They are transmitted differently. They reproduce differently. They cause illness differently.

How similar are HIV and SARS-CoV-2?

A few recent studies on the effects of HIV and SARS-CoV-2 indicate that they have some similarities. Shanghai-based researchers have provided evidence that SARS-CoV-2 can infect T cells, the same cells targeted by HIV. Other researchers have documented that people with severe COVID-19 may have lymphopenia, or an abnormally low number of lymphocytes in the blood. Likewise, infection with HIV causes this abnormality, possibly causing the immunosuppression associated with AIDS. But these results should not lead us to assume that SARS-CoV-2 is like HIV.

Let’s first look at the infection of T lymphocytes, or white blood cells. The authors of this report provide evidence that SARS-CoV-2 can infect certain white blood cells in the laboratory. They also noted that MERS-CoV, a virus closely related to SARS-CoV-2, can infect these same cells. Importantly, however, they noted that neither MERS-CoV nor SARS-CoV-2 demonstrated an ability to replicate in these cells. It seems that these viruses can enter cells, but the infection is aborted. HIV, on the other hand, replicates aggressively in white blood cells, with infected cells spitting out thousands of new viral particles.

What about the observed lymphopenia? In a study of people who died from COVID-19, researchers noted that the amount of lymphocytes in the blood decreased steadily during the course of the disease. In contrast, other standard blood markers, such as the number of red blood cells, have remained fairly constant. Does this observation mean that infection with SARS-CoV-2 leads to immunosuppression, like HIV? Not necessarily. The authors note that several[1] factors could lead to lymphopenia. Instead, they pointed out that monitoring lymphocyte levels in people with COVID-19 can be an effective and easy way for clinicians to predict the severity of the disease.

Is there anything we can learn about HIV by trying to develop a vaccine?

Perhaps the most important lesson is that vaccine development can be tricky. At a very basic level, vaccination mimics a natural process by intentionally exposing the body to something resembling a pathogen. The vaccine can be an inactivated or weakened form of the pathogen or a protein isolated from it. In response, the body produces antibodies and cytotoxic white blood cells that can effectively fight off the true pathogen, if it ever enters the body.

HIV thwarts this seemingly simple process in several ways. First, HIV mutates rapidly, constantly changing in appearance and staying one step ahead of any response produced by the body. Second, the HIV genome, when it enters a cell, integrates with the genome of the host cell, making itself invisible to the host’s immune response. Third, HIV is not particularly immunogenic, which means that our bodies do not naturally develop an effective immune response against it. These attributes of HIV have thwarted all efforts to develop an effective vaccine.

Here’s the good news: Coronaviruses have a much lower spontaneous mutation rate than HIV. Preliminary data suggests that this property is true for SARS-CoV-2. It is also known that the SARS-CoV-2 genome does not integrate into the genomes of infected cells. Finally, previous research on coronaviruses indicates that humans develop a strong immune response to these viruses.

Unfortunately, there is also bad news. Attempts to develop a vaccine against SARS-CoV-1 after the 2003 SARS epidemic were unsuccessful. Several candidate vaccines have been shown to be relatively effective when tested in animals. But the vaccinated animals also had severe immunopathology – the vaccine appeared to have caused the animals’ immune systems to become overactive and cause them further damage. More recently, researchers have shown in the same way that a candidate vaccine against MERS-CoV provided protection to mice against the virus, but could also cause the same type of serious damage to their immune system.

What about vaccines in development?

There are many candidate vaccines in the works for SARS-CoV-2, the virus that causes COVID-19. Several of them have already entered phase I human trials. Indeed, trials involving a candidate vaccine based on mRNA developed by the biotechnology company Moderna began on March 16, 2020, less than three months after Chinese authorities reported the first cases of the emerging disease. Most likely, several of these candidates will induce a reasonable immune response. But will they be safe and effective? Only extensive testing and human trials will provide the answer to this important question.

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