Antibody clues in animal trials raise vaccine hopes

Sufficient quantities of antibodies and T cell response are able to stop macaques from being infected by the Sars-Cov-2, a comparative animal trial to study thresholds of immune response and its effects has found, offering clues that predict vaccines are likely to succeed but will need to trigger strong responses.

These clues also include the nature of immune response that plays a role: it’s not merely antibodies that play a part but also how T cells respond. T cells destroy infected cells, while antibodies bind to circulating viruses and neutralise them. In macaques, the researchers found, depleting the T cells led to lower levels of antibodies too.

The resulting findings, taken together, provide a key proof-of-concept that antibodies can protect against Sars-Cov-2 infection and if they are near or below the threshold required for protection, cellular immune response (T cells) may be important in controlling the virus, the authors led by Harvard University’s Katherine McMahan and Jingyou Yu said in their study, which was published in Nature on Friday after peer review.

“Our data suggest the importance of Sars-Cov-2 vaccines to induce potent and durable humoral as well as cellular immune responses,” they added.

The researchers used rhesus macaques – medical experiments on primates typically predict responses that might also take place in humans – and injected them with antibody-rich plasma in varying doses from other recovered monkeys.

Over a period of two weeks, the group that had the highest dose of plasma – 250 mg/kg of weight – did not test positive for the virus in samples from lungs as well as swabs from deep within the nose and throat. The macaques were split into groups of three and only one among the three that got the second-highest dose, 25mg/kg, tested positive.

All three that got the lowest of the plasma dose – 2.5mg/kg -- tested positive as did the three that got no plasma. But even the one group with the least amount of plasma showed a lower viral load than the control group.

The researchers used these findings to quantify the threshold of antibody concentration that appeared to be most effective. “In particular, NAb titers (concentration of neutralising antibodies) of approximately 500 fully protected, and titers of approximately 50 partially protected the macaques,” said the peer reviewed study published in Nature on Friday.

These concentrations, the researchers added, “are comparable to those observed in convalescent macaques and are readily achievable by vaccination in humans”.

The researchers also determined that in addition to antibodies, another aspect of the immune system plays a part: CD8 T cells, which are also known as killer T cells. “CD8 depletion studies also showed that cellular immunity can contribute to protection against SARS-CoV-2 re-challenge in convalescent macaques with waning antibody titers,” the report said.

The authors determined this by injecting 13 macaques with anti-CD8 antibodies. Four weeks after they were exposed to Sars-Cov-2, all of these monkeys developed an infection with lower levels of antibodies compared to the control group animals in the other group.

“These data indicate that relatively low titers of antibodies are sufficient for protection in both the upper and lower respiratory tracts. CD8 depletion studies also showed that cellular immunity can contribute to protection against SARS-CoV-2 re-challenge in convalescent macaques with waning antibody titers,” the authors said.

A third finding in the study related to the use of convalescent plasma – the researchers determined that plasma that is highly rich in antibodies seemed to work better. “Our data should be interpreted cautiously, because only high serum NAb titers in recipient animals (approximately 500) showed therapeutic efficacy in this model, whereas lower serum NAb titers in recipient animals approximately 50) did not have detectable efficacy. Such high serum NAb titers in recipient macaques likely exceed typical serum NAb titers achieved in human recipients of convalescent human plasma,” they said.