Vaccine candidates for COVID-19 should elicit a broad immune response that includes antibodies, and the body’s helper and killer T cells, according to a study which says weak or uncoordinated immunity may lead to a poor disease outcome.
The research, published in the journal Cell, confirms that a multi-layered, virus-specific immune response is important for controlling the novel coronavirus during the acute phase of the infection and reducing COVID-19 disease severity.
“Our observations could also explain why older COVID-19 patients are much more vulnerable to the disease,” said study senior author Shane Crotty from the La Jolla Institute for Immunology in the US.
“With increasing age, the reservoir of T cells that can be activated against a specific virus declines and the body’s immune response becomes less coordinated, which looks to be one factor making older people drastically more susceptible to severe or fatal COVID-19,” Crotty said.
In the research, the scientists collected blood samples from 50 COVID-19 patients, and analysed multiple branches of their immune system — novel coronavirus specific antibodies, helper and killer T cells.
“It was particularly important to us to capture the whole range of disease manifestation from mild to critically ill so we could identify differentiating immunological factors,” said study co-author and infectious disease specialist Sydney Ramirez.
The researchers found that all fully recovered individuals had measurable antibody, helper and killer T cell responses against the novel coronavirus SARS-CoV-2.
However, they said the response varied widely in acute COVID-19 patients, with some lacking neutralising antibodies, others helper or killer T cells or any combination thereof.
“When we looked at a combination of all of our data across all 111 measured parameters we found that in general, people who mounted a broader and well-coordinated adaptive response tended to do better,” said Carolyn Moderbacher, another co-author of the study from La Jolla Institute for Immunology.
“A strong SARS-CoV-2 specific T cell response, in particular, was predictive of milder disease. Individuals whose immune response was less coordinated tended to have poorer outcomes,” Moderbacher said.
The scientists found that the effect was magnified when they broke down the dataset by age.
“People over the age of 65 were much more likely to have poor T cell responses and a poorly coordinated immune response, and thus have much more severe or fatal COVID-19,” Crotty said.
The scientists explained that as people age, the immune system’s supply of deployable immature T cells dwindles, with fewer cells available to be activated to respond to a new virus.
“This could either lead to a delayed adaptive immune response that is unable to control a virus until it is too late to limit disease severity or the magnitude of the response is insufficient,” Moderbacher said.
The scientists believe T cells, and helper T cells in particular, are associated with better protective immune responses.
“This was perplexing to many people, but controlling a primary infection is not the same as vaccine-induced immunity, where the adaptive immune system is ready to pounce at time zero,” Crotty said.
“Thus, these findings indicate it is plausible T cells are more important in natural SARS-CoV-2 infection, and antibodies more important in a COVID-19 vaccine,” he said.
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