OHSU researchers find immune response to COVID-19 strengthens over time
Study suggests people who have had COVID-19 benefit from vaccination, even if they’ve delayed it
Peer-Reviewed PublicationImmunity from COVID-19 appears to gather strength with more time between vaccination and infection, a new laboratory study from researchers at Oregon Health & Science University suggests. The findings carry implications for vaccine recommendations as the pandemic transitions to an endemic state.
Researchers measured the antibody response in blood samples for a group of people who gained so-called “hybrid immunity” through two means: either vaccination followed by a breakthrough infection, or by getting vaccinated after contracting COVID-19. They measured the immune response in blood samples of 96 generally healthy OHSU employees and found that the immune response was uniformly stronger the longer the time period between vaccination and infection. The longest interval measured was 404 days.
Their findings suggest that vaccine boosters should be spaced no more frequently than a year apart, at least among healthy people.
“Longer intervals between natural infection and vaccination appear to strengthen immune response for otherwise healthy people,” said co-senior author Fikadu Tafesse, Ph.D., associate professor of molecular microbiology and immunology in the OHSU School of Medicine.
The study comes as an advisory panel for the Food and Drug Administration is due to meet Thursday, Jan. 26, to consider the nation’s COVID-19 vaccine strategy going forward.
Published in the Journal for Clinical Investigation Insight, the new research is the latest in a series of laboratory discoveries by OHSU scientists revealing a pattern of strengthened immune response through hybrid immunity. Their findings suggest that the magnitude, potency and breadth of hybrid immune response all increased with a longer time period between exposure to the virus — whether through vaccination or natural infection.
This likely is related to the body’s immune response maturing over time, said co-senior author Marcel Curlin, M.D., associate professor of medicine (infectious diseases) in the OHSU School of Medicine and medical director of OHSU Occupational Health.
“The immune system is learning,” Curlin said. “If you’re going to amplify a response, what this study tells us is that you might want to boost that response after a longer period of learning rather than early after exposure.”
Further, the research team found that it didn’t matter whether someone developed hybrid immunity by getting vaccinated after contracting COVID-19 or after a breakthrough infection following vaccination. Both groups developed an equally potent immune response.
The findings suggest long-lasting potency of so-called “memory cells,” the B cells that recognize an invading virus and generate protein antibodies to neutralize the virus and its many variants. The authors write that an ever-growing pool of people who have contracted the SARS-CoV-2 virus stand to benefit from vaccination, even if they’ve delayed it until now.
Relying on natural infection alone is a bad idea, “given the risks of severe illness, long-term complications, and death,” the authors write.
The researchers say the findings are the latest to point toward the virus evolving to an endemic state.
“Our results point to a future where inevitable vaccine breakthrough infections would be expected to help build a reservoir of population-level immunity that can help blunt future waves and reduce the opportunity for further viral evolution,” they write.
The researchers cautioned that the immune response was measured in relatively healthy people, and boosters may be advisable on a more frequent basis among vulnerable people who are older or are immunocompromised.
Funding for this study was supported by the M.J. Murdock Charitable Trust; the OHSU Foundation; the National Institutes of Health training grant T32HL083808; NIH grant R01AI145835; and a grant from the OHSU Innovates IDEA fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
JOURNAL
JCI Insight
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
An extended interval between vaccination and infection enhances hybrid immunity against SARS-CoV-2 variants
ARTICLE PUBLICATION DATE
26-Jan-2023
Children’s immune response to coronavirus: fast but doesn’t last
Children have a strong initial immune reaction to coronavirus, but don’t transfer this to long-lasting memory T cells like adults do, new research shows
Peer-Reviewed PublicationIMAGE: GRAPHIC OF CORONAVIRUS, SARS-COV-2 CELLS. view more
CREDIT: GARVAN INSTITUTE OF MEDICAL RESEARCH
Children have largely avoided severe COVID-19 symptoms because they have a strong initial ‘innate’ immune reaction that quickly defeats the virus. And now, researchers led by scientists at the Garvan Institute of Medical Research have uncovered what this might mean for the immune system. Unlike those of adults, children’s immune systems don’t remember the virus and don’t adapt, so when they’re next exposed to SARS-CoV-2, their body still treats it as a new threat, the scientists found.
“The price that children pay for being so good at getting rid of the virus in the first place is that they don’t have the opportunity to develop ‘adaptive’ memory to protect them the second time they are exposed to the virus,” says lead author Professor Tri Phan, Head of the Intravital Microscopy and Gene Expression (IMAGE) Lab and Co-Lead of the Precision Immunology Program at Garvan.
“Because children haven’t been exposed to many viruses, their immune system is still ‘naive’. And because they don’t develop memory T cells, they are at risk of getting sick when they become reinfected. With each new infectious episode as they get older, there is a risk of their T cells becoming ‘exhausted’ and ineffective, like the T cells in older people. This is why we think it’s important to vaccinate children,” he says.
The immune system has two modes. The innate immune system is the first line of defence, comprising physical barriers such as skin and mucosal surfaces that block viruses from entering. It is also composed of cells that make chemicals to signal to other cells and ward off the viruses. The innate immune system does not distinguish between one type of virus or another.
The second line of defence comprises B and T cells of the adaptive immune system. These cells have specific receptors that can recognise and distinguish different parts of a virus and generate a rapid response to neutralise or limit it.
Infants start with an immune system blank slate, which has a much higher proportion of naïve T cells, the researchers found. As they move through childhood into adulthood and become exposed to more viruses, the naïve T cells are replaced by memory T cells that are locked in to making responses to viruses they have seen before.
“Over time, as you get infections, your immune system becomes more ‘educated’, allowing you to make a faster immune response that’s tightly matched to the viruses that have infected you before,” says Associate Professor Philip Britton, paediatric infectious diseases physician at the Children’s Hospital at Westmead, and clinical lead in the study. “Children’s immune systems move from relying mostly on the innate system, to needing the adaptive system as a backup as they grow older and are unable to clear viruses as rapidly.”
In the new study, published in the journal Clinical Immunology, Professor Phan, Associate Professor Britton and colleagues took a deep dive to investigate T cells and cellular immune responses of a small group of children and their household family contacts who had mild or no symptoms from coronavirus (SARS-CoV-2) infection.
The researchers sequenced white blood cell samples to analyse T cells in children and adults at the time of acute infection and one month later.
Because they studied household family contacts who were infected, researchers could control for the impact of genetic or environmental influences on the immune response.
They found that children had many different naive T cells to fight SARS-CoV-2 and made poor memory T cell responses to the virus after they had recovered, whereas the adults had few naïve T cells but made good memory T cell responses after recovery.
Interestingly, the findings point to why older adults can have a kind of immune over-reaction to SARS-CoV-2.
“When adults are infected for the first time with SARS-CoV-2, their memory T cells recognise only what they’ve seen before – like a familiar part of the coronavirus that is shared with the common cold coronaviruses,” Professor Phan says.
“This may lock the immune system in to a misdirected response that is not specific to SARS-CoV-2. It provides an opportunity for the virus to escape and multiply unchecked to cause more severe symptoms as the immune system ramps up to try and fix the problem.”
Professor Tri Phan is a Conjoint Professor at St Vincent's Clinical School, UNSW Medicine and Health
This research was supported by:
Mrs Janice Gibson and the Ernest Heine Family Foundation
National Health and Medical Research Council (NHMRC)
UNSW Cellular Genomics Futures Institute and UNSW Scientia PhD Scholarship
Garvan Institute COVID Catalytic Grant, UNSW COVID-19 Rapid Response Research Initiative
National Institutes of Health Centers of Excellence for Influenza Research and Response (CEIRR) COVID-19
Snow Medical Foundation BEAT COVID-19
Griffith University
JOURNAL
Clinical Immunology
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19
No comments:
Post a Comment