Changing when a vaccine booster dose is given can have a major effect on how immune responses are triggered, according to new research from University of Oxford scientists.
The findings are published today in the journal Science Immunology.
The team of scientists, based at the University of Oxford’s Pandemic Sciences Institute, Oxford Vaccine Group and Experimental Medicine Division, studied a group of healthcare workers who received two COVID-19 vaccines during the initial vaccine rollout – the Pfizer BNT162b2 mRNA vaccine and the Oxford/AstraZeneca ChAdOx1 nCoV-19 vaccine.
The researchers explored the immune signals occurring within one day after the first vaccine dose and the second booster dose, to understand how vaccination is initially triggering the immune system. They specifically focused on T cell immunity, which works together with antibodies to protect people against viruses.
Despite extensive studies of these vaccines, gaps in understanding around early immune responses and T cell immunity still exist.
Key findings
Researchers found that for the Pfizer mRNA vaccine, the booster dose more strongly turned on the early immune response than the first dose, and this was linked to the activation of so-called “unconventional” T cells in the blood.
In contrast the Oxford/AstraZeneca vaccine triggered these unconventional cells very strongly after the first dose.
These specialised cells pick up early signals and act as powerful “amplifiers” to create a much bigger early immune reaction. This early immune activation is what contributes to early side effects that individuals experience after vaccination.
By extending the interval between mRNA vaccine doses (from around 3 weeks to 3 months), this early reaction of “unconventional” T cells was reduced, and this was linked to a reduction in the early symptoms the recipients experienced (reactogenicity) after the booster.
In parallel, the team of scientists also studied the impact of the different vaccines on the protective immune response they induced against the virus. The team used a new test that was able to pick up many different types of T cell responding to the vaccine.
The type of long-term protective “memory” immune response made was also strongly influenced by the interval between vaccine doses, and the longer interval between doses was associated with cells better able to respond to future booster vaccines.
This shows that the earliest events occurring after vaccination – especially how strongly the unconventional cells are fired up on the first day – imprints itself on the immune system. How the responding T cells are “born” has a long-term impact on how they later behave.
Professor Paul Klenerman, Investigator at the Pandemic Sciences Institute at the University of Oxford and one of the lead authors said: “These studies have shown the very first responses the body makes to these vaccines, and how these early events have an impact on long-term immunity.
“Unconventional T cells act like the 'guard dogs' of the immune system – picking up the very earliest scent of a vaccine or infection and quickly and loudly alerting the rest of the immune system. Now we know what scents they pick up, how they bark, and what the impact is.
“Harnessing this superpower of unconventional T cells could help boost immunity to a range of infections.
“Something as simple as changing when a booster dose is given can have a major effect on how all these immune responses are triggered. Understanding that will help us design future vaccination programmes for different diseases.”
Implications of the research
These studies show how sensitive the body is to the timing of vaccine doses, as well as the type of vaccine.
They also reveal how important certain types of unconventional T cell are in responses to vaccines and viruses.
Such cells – including an abundant cell called a “MAIT” (Mucosa Associated Invariant T) cell – are often overlooked but appear to play a crucial part in alerting and activating the rest of the immune system.
This work may help in the design of new vaccine programmes for a range of diseases, to maximise the long-term immune response while minimising the early side-effects. In future it may also be possible to predict how different individuals might respond and tailor such vaccines accordingly.
Nick Provine, Career Development Fellow at the Pandemic Sciences Institute at the University of Oxford and one of the lead authors said: “These findings increase our understanding of how time between vaccine doses can impact on both the unwanted side-effects (reactogenicity) and desired protective immunity.
“Prior studies, including a study from the University of Oxford, have shown that increased time between first and second dose of the Pfizer BNT162b2 mRNA vaccine increases antibody responses.
“Our work now shows why this increased interval reduces unwanted side effects and improves T cell immunity. These findings collectively suggest dosing regimens should be carefully considered in the design of future mRNA-based vaccines.”
Read the full papers in Science Immunology: