Targets & Mechanisms
Primate study reveals relationship between neutralizing antibodies and T cell responses
A rhesus macaque study argues that CD8+ T cells contribute to immunity against COVID-19, while simultaneously suggesting that antiviral antibodies alone, if at a high enough titer, can protect against SARS-CoV-2.
Predictions about correlates of protection for COVID-19 have primarily focused on neutralizing antibody levels, as much less is known about whether and to what degree CD8+ T cells contribute to immunity.
In a Nature article published Dec. 4, a team led by Dan Barouch at the Beth Israel Deaconess Medical Center solidified a role for CD8+ T cells by depleting the immune cells from rhesus macaques after the animals had recovered from SARS-CoV-2 infection. Exposing the monkeys to the virus a second time revealed their defenses had been weakened, even though they still produced neutralizing antibodies.
Among the re-infected monkeys depleted of CD8+ T cells, 25% had detectable virus in lung fluid and all had positive nasal samples. By contrast, none of the re-infected control animals had positive lung fluid samples, and only one of five had detectable virus in the nose.
Nasal viral loads in the CD8+ T cell-depleted monkeys — though lower than in animals infected for the first time — were higher than macaques that had not been depleted of CD8+ T cells.
Despite this clear role for CD8+ T cells, the team also showed that the cells were not necessary for protection, if the animals had sufficiently high levels of neutralizing antibodies.
The researchers treated monkeys naïve to SARS-CoV-2 with different doses of antibodies purified from recovered animals, and then challenged them with virus. The highest dose, in which neutralization titers were 511-571, completely prevented viral detection in nose and lung fluid samples; whereas the two lower doses, in which titers were 42-49 and <20-23, provided partial protection.
Data from the monkeys cannot be extrapolated to predict how much protection humans derive from CD8+ T cells, or from specific levels of neutralizating antibodies — that information will require immunogenicity and efficacy data to become available from clinical trials.
But the monkey study does suggest vaccine efficacy won’t be determined by strict thresholds of humoral or cellular immunogenicity. Instead, it’s likely that the threshold for one depends on the other, meaning there will be multiple combinations of neutralizing antibodies and T cell activation levels that effectively prevent COVID-19. For example, a vaccine that induces lower neutralization titers could be as effective as one that induces higher titers, if if activates stronger T cells responses.