mRNA COVID-19 vaccines offer ‘quite encouraging’ long-term protection
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mRNA vaccines yielded not only strong short-term immune response against COVID-19, but also persistent immunity through at least 6 months, said a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
“This virus prompted fears of whether people developed adaptive immune response at all,” Shane Crotty, PhD, professor at the Center for Infectious Disease and Vaccine Research at the LaJolla Institute for Immunology in California. “[We started studying] this well before vaccines were developed at all.”
In his lab work, Crotty has spent significant time simply understanding the nature of the three branches of immunity — B-cells, CD4 T-cells and CD8 killer T-cells — and the role they play in battling COVID-19. “The founding principle of my lab is to understand the immunology of this and improve upon it.”
One of the key questions is how long immunological memory lasts after a person has been infected with the virus, which largely involved measuring levels of those different types of cells at various time points. “Immunological memory in humans is difficult to predict,” he said.
The heterogeneity of immune memory from person to person has a “1,000-fold range” for the cellular parameters that Crotty has assessed in his lab.
Armed with this backdrop of knowledge, Crotty then turned to COVID-19 vaccines.
“The RNA vaccines have been incredibly successful and clearly elicited really good short-term neutralizing antibody responses and clearly were capable of eliciting T-cell responses,” Crotty said. What is less certain is how well they elicited T-cell memory or CD8 T-cell responses. “Those are the questions we wanted to answer.”
In an early study of a reduced-dose vaccine published in Science, Crotty and colleagues determined that antibodies declined approximately 10-fold by approximately 6 months after the second dose.
However, CD4 T-cell numbers declined only about two-fold after the second dose. “We thought this was quite encouraging,” Crotty said.
As for CD8 T-cells, approximately two-thirds of individuals experienced just a two-fold decline at 6 months. “Again, we thought this was a pretty amazing result for an mRNA vaccine,” Crotty said.
Regarding the question of whether T cells are recognizing variants, Crotty suggested that previous COVID-19 infection may provide some CD4 and CD8 T-cell response. However, further data on the nature of this response. He suggested that T-cell recognition of omicron is “sustained.”
If there is a final factor for consideration, it is the number of exposures to COVID-19 in some form. “Multiple exposures, either from hybrid immunity or multiple vaccines, is good,” Crotty said. “Your immune system is good at recognizing variants.”
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Crotty S. RJ Fasenmyer Center for Clinical immunology Annual Lectureship: Understanding immunity and immune memory to SARS-CoV-2 and the potential of broad coronavirus vaccines. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 26, 2022. (virtual meeting).
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