New Research Uncovers Potential Explanation for COVID Vaccine Blood Clot Connection

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

A recent study conducted by a team from SAHMRI and Flinders University in Australia has revealed significant variations in the way the AstraZeneca and Pfizer COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>COVID-19 vaccines affect the immune system. The findings, published in Cell Reports<em>Cell Reports</em> is a peer-reviewed scientific journal that published research papers that report new biological insight across a broad range of disciplines within the life sciences. Established in 2012, it is the first open access journal published by Cell Press, an imprint of Elsevier.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Cell Reports Medicine, are part of the COVID-19 Vaccine Immune Responses Study (COVIRS) and were based on the analysis of the immune responses of 102 adults of various ages residing in South Australia, where there was no SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>SARS-CoV-2 community transmission at the time of the study.

The participants in the study had their blood samples collected immediately after receiving each dose of either the Oxford/AstraZeneca or Pfizer/BioNTech COVID-19 vaccine, in order to evaluate their early immune response. Further tests were conducted 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 alike in the sense that they induce the immune system to recognize and protect against the SARS-CoV-2 virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>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 SAHMRI’s Systems Immunology Laboratory and Flinders UniversityFounded in 1966, Flinders University is a public university in Adelaide, South Australia. It was named in honor of British navigator Matthew Flinders, who explored and surveyed the South Australian coastline in the early 19th century.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Flinders University Professor David Lynn led the study, using a method of biological analysis known as ‘multi-omics’ to examine immune responses in many different ways in thousands of blood samples. Professor Lynn says this comprehensive analysis of immune responses to these different vaccines has revealed lots of new information that’ll help inform future vaccine design.

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

“This response is targeted against the adenovirus vector in the vaccine, not the Spike protein and the intensity of this response correlates with the expression of proteins that act as a pre-cursor 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 connection between the Oxford/AstraZeneca vaccine and the cases of VITT that have been reported.”

The study also found those who’d only had two doses of the Oxford/AstraZeneca vaccine generally produced lower amounts of antibodies and less of a specialized type of T-cell that helps with antibody production; compared to those who had two doses of the Pfizer/BioNTech vaccine.

However, this was rectified once they had their third booster dose of an mRNA vaccine, illustrating the importance of booster doses. The study added evidence to the notion 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 lower immune response after two doses. Fortunately, a third booster dose was highly effective at overcoming this. Immune responses induced immediately after vaccination predicted the subsequent B and T cell response to the vaccine measured a month later.

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

A further surprise to researchers was the finding that feeling unwell after a vaccine dose may in fact be linked to its effectiveness.

“People who showed 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 efficacy as they can directly kill viral cells,” Professor Lynn said.

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

Reference: “A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored 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 E.L. 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, 16 February 2023, Cell Reports Medicine.
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 wishes to express its gratitude to all participants and funders, including Bioplatforms Australia, AstraZeneca, The Hospital Research Foundation and the Flinders Foundation.