Science on the Attack: The Hunt for a Coronavirus Vaccine (2)

In the previous post, we saw how three different types of coronavirus vaccine, all based on established technologies, are under development: virus (killed or attenuated live), viral vector, and protein-based vaccines. Here I review experimental genetic vaccines for SARS-CoV-2, which rely on protective antibody production – like the other three do; and T-cell-inducing vaccines, a newcomer approach which arouses a massive army of those immune system warriors, T cells.

Genetic vaccines, sometimes called nucleic acid vaccines, utilize part of the coronavirus’s genetic code to deliver the genetic instructions for a coronavirus protein such as the spike protein, right into human cells. In this seemingly risky move, the cells read the instructions and crank out copies of the viral protein, but not of the whole virus as infected cells do – and thus don’t cause disease. The protein copies stimulate antibody generation, just like the viral protein fragments or shells in protein-based vaccines.

The genetic instructions can be in the form of either DNA or RNA. For DNA vaccines, an engineered loop of coronavirus protein DNA is inserted into cells, which then employ their own messenger RNA to assemble the viral proteins. RNA vaccines deliver synthetic viral messenger RNA directly into cells. An advantage of genetic vaccines is that they can be produced more rapidly than their traditional counterparts.

Other DNA vaccines have been approved for animal diseases such as West Nile virus in horses, and a DNA coronavirus vaccine based on the spike protein has been found to protect monkeys. But no DNA coronavirus vaccines so far have approval for human use. The same is true for RNA coronavirus vaccines, although biotech company Moderna recently obtained promising results in a small trial of coronavirus vaccine safety. 

T-cell vaccines have gained attention because of emerging evidence that many people may already have immune cells capable of recognizing the SARS-CoV-2 virus and warding it off. This extraordinary degree of protection is thought to come from T cells, not antibodies. Although studies have found that antibodies against the deadly coronavirus dissipate fairly quickly, T cells are able to remember past infections and kill pathogens if they reappear, even after long periods of time. A recent research paper reported that up to 50% of people who had never been exposed to the virus had high levels of SARS-CoV-2-specific T cells, a finding replicated in other studies.

Like many advances in science, this particular discovery was accidental. The paper’s authors were conducting an experiment with COVID-19 convalescent blood and needed a control blood sample for comparison. After choosing blood samples collected from healthy residents of San Diego between 2015 and 2018, several years before the current pandemic began, they found to their surprise that about half the samples showed strong T-cell reactivity against the virus.

The authors speculated that this T-cell recognition of the SARS-CoV-2 virus may come partly from previous exposure to one of the four known coronaviruses that cause the common cold and circulate widely among humans. If so, the discovery paves the way to a new type of vaccine, similar to those being used against certain cancers such as melanoma. However, the authors emphasized that the data hadn’t yet demonstrated the source of the T cells or whether they are actually memory T cells.

Memory T cells are the third type of T cell, in addition to helper T cells known as CD4+ cells that identify antigens, or viral protein fragments, and killer T cells that devour virus-infected cells. T-cell memory of past diseases is long lasting, up to decades. People who recovered from SARS, the disease most closely related to COVID-19, still show cellular immunity to that coronavirus after 17 years.

CREDIT: WIKIPEDIA COMMONS

An even more recent study appears to confirm the hypothesis that the observed T-cell response results from previous exposure to common cold coronaviruses. Should this turn out to be the case, it could explain the puzzle of why COVID-19 is much more severe in some people than in others: those who have recently wrestled with the common cold may have an easier time battling a more vicious member of the coronavirus family, and may get less sick. On the other hand, much is still unknown and pre-existing T cells could even interfere with other immune system responses.

As for a coronavirus vaccine, recent Phase III clinical trials have shown the efficacy of potential T-cell-inducing vaccines for diseases such as malaria and HIV. But nothing is yet licensed, so development of a coronavirus T-cell vaccine is unlikely in the short term.

Next: It’s Cold, Not Hot, Extremes That Are on the Rise