New research reveals potential explanation for COVID vaccine blood clot connection

A recent Australian study found fundamental differences in immune responses between AstraZeneca and Pfizer COVID-19 vaccines. The AstraZeneca vaccine elicited an unexpected memory-like response, potentially explaining its rare association with blood clotting, while the Pfizer vaccine induced stronger B and T cell activity. Booster doses, especially those of mRNA , have been shown to be crucial in enhancing immune responses.

Scientists identify key differences in immune responses to AstraZeneca and Pfizer vaccines.

A recent study conducted by a team from SAHMRI and flinders university in Australia revealed significant variations in the way AstraZeneca and Pfizer COVID-19 vaccines affect the immune system. The findings, published in Cell reports Medicineare part of the COVID-19 Vaccine Immune Responses Study (COVIRS) and were based on analysis of the immune responses of 102 adults of varying ages residing in South Australia, where there were no SARS-CoV-2 community transmission at the time of the study.

Study participants had their blood samples drawn immediately after receiving each dose of the Oxford/AstraZeneca or Pfizer/BioNTech COVID-19 vaccine, to assess their early immune response. Further tests were carried out 28 days after each immunization to measure the activity of B and T cells, both of which play a crucial role in the immune response. B cells produce antibodies, while T cells target and eliminate infected cells.

The vaccines are similar in that they trick the immune system into recognizing and protecting against SARS-CoV-2 virus, but they differ in how this is achieved. The Pfizer vaccine uses mRNA technology to induce host cells to produce the SARS-CoV-2 Spike protein, while the AstraZeneca vaccine uses a harmless virus (a chimpanzee adenovirus) to encode the Spike protein.

Head of the SAHMRI Systems Immunology Laboratory and flinders university Professor David Lynn led the study, using a method of biological analysis known as “multi-omics” to examine immune responses in different ways in thousands of blood samples. Professor Lynn says this comprehensive analysis of immune responses to these different vaccines has revealed a lot of new information that will help inform future vaccine design.

“After the first dose, we were surprised to find that the Oxford/AstraZeneca vaccine elicits an unexpected memory-like response in the immune system, recognizing the vaccine as if it were something it had seen before” , says Professor Lynn, of the College of Medicine and Public Health at Flinders University.

“This response is targeted against the adenoviral vector in the vaccine, not against the Spike protein and the intensity of this response correlates with the expression of proteins that act as a precursor to thrombosis or blood clotting. While vaccine-induced immune thrombotic thrombocytopenia (VITT) is an extremely rare side effect associated with the Oxford/AstraZeneca vaccine that none of the participants developed during the study, this research offers a potential explanation for the link between the Oxford/AstraZeneca vaccine and the reported VITT case.

The study also found that those who received only two doses of the Oxford/AstraZeneca vaccine generally produced lower amounts of antibodies and less of a specialized type of T cell that helps in antibody production; compared to those who had received two doses of the Pfizer/BioNTech vaccine.

However, this was rectified once they received their third booster dose of an mRNA vaccine, illustrating the importance of booster doses. The study added evidence to the idea that COVID-19 vaccines offer some people more effective protection than others.

The reasons for this variability are not well understood, but Professor Lynn says age is a factor, with older people generally having a weaker immune response after two doses. Fortunately, a third booster dose was very effective in overcoming this. Immune responses elicited immediately after vaccination predicted the subsequent B and T cell response to the vaccine measured one month later.

“One to two days after the initial vaccination, we measured gene expression responses in the blood that correlated with adaptive immune responses that provide protection 28 days later,” says Professor Lynn.

Another surprise for researchers was the finding that feeling unwell after a vaccine dose may actually be linked to its effectiveness.

“People who had symptoms of fatigue and fever immediately after the third dose were more likely to have better T-cell responses. T-cells play a vital role in vaccine effectiveness because they can directly kill cells viral,” Professor Lynn said.

Overall, this project has provided important new insights into early immune responses to these vaccines and offers a better understanding of how they work to protect against COVID-19.

Reference: “A systemic immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vector vaccines” by Feargal J. Ryan, Todd S. Norton, Conor McCafferty, Stephen J. Blake, Natalie E. Stevens, Jane James, Georgina L. Eden, Yee C. Tee, Saoirse C. Benson, Makutiro G. Masavuli, Arthur EL Yeow, Arunasingam Abayasingam, David Agapiou, Hannah Stevens, Jana Zecha, Nicole L Messina, Nigel Curtis, Vera Ignjatovic, Paul Monagle, Huyen Tran, James D. McFadyen, Rowena A. Bull, Branka Grubor-Bauk, Miriam A. Lynn, Rochelle Botten, Simone E. Barry, and David J. Lynn, February 16 Medicine Reports Unit.
DOI: 10.1016/j.xcrm.2023.100971

The study was a major collaboration involving SAHMRI, Flinders University, Murdoch Children’s Research Institute, The University of Melbourne, The University of Adelaide, Basil Hetzel Institute for Translational Health Research, University of New South Wales, The Kirby Institute, Alfred Hospital, Monash University, AstraZeneca and the Royal Adelaide Hospital.

The team would like to express their gratitude to all participants and funders, including Bioplatforms Australia, AstraZeneca, The Hospital Research Foundation and the Flinders Foundation.