Single dose of Oxford–AstraZeneca COVID vaccine shown to be more immunogenic than natural infection

By investigating antibody and T cell responses to a single dose of the Oxford–AstraZeneca COVID-19 vaccine, researchers from Sri Lanka and the United Kingdom have found that more than 90% of vaccinated individuals produced an adequate amount of antibodies after receiving only one dose of the vaccine – irrespective of their age and gender. Their paper is currently available on the medRxiv* preprint server.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In order to enter the cell, the receptor-binding domain (RBD) of the spike glycoprotein of this virus is known to attach to the angiotensin-converting enzyme 2 (ACE2) receptor.

Due to such pivotal role of the spike glycoprotein, it is of no wonder that it represents the main target for antibody-mediated neutralization. And while most of the vaccines for preventing COVID-19 are two-dose vaccines, some vaccines (such as the Johnson and Johnson adenoviral vector vaccine solution) comprise a single dose.

However, we are not sure whether a single dose of Oxford–AstraZeneca and Pfizer-BioNTech vaccines can also be protective enough; furthermore, many variants of concern with mutations in the spike glycoprotein have emerged, increasing in turn disease transmission and potentially affecting vaccine efficacy.

In order to appraise the immunogenicity of a single dose of the Oxford–AstraZeneca COVID-19 vaccine in a real-world setting, a research group (led by Dr. Chandima Jeewandara from the University of Sri Jayewardenepura) assessed antibody and T cell responses in a large cohort of health care workers in Sri Lanka.

Appraising antibody and T cell responses

The study population consisted of 607 naïve and 26 previously infected health care workers 28 to 32 days after a single dose of the vaccine. None of the study participants reported having COVID-19 infection during this one month.

Hemagglutination tests for antibodies to the RBD of the wild-type virus, UK variant (B.1.1.7) and South African variant (B.1.351), as well as the surrogate neutralization assay, have all been carried out in 69 naïve and 26 previously infected individuals.

Finally, specific T cell responses for spike protein (with S1 and S2 pools S1) were measured by the ex vivo enzyme-linked immunospot interferon-gamma assays in 76 study subjects by using freshly isolated peripheral blood mononuclear cells.

An abundance of antibodies

This study has shown that 92.9% of previously naïve individuals actually seroconverted to a single dose of the vaccine, irrespective of their gender and/or age. In other words, a single dose produced a high amount of ACE2 blocking antibodies (detected in 97.1% of naïve vaccine recipients), as well as those aimed towards RBDs of SARS-CoV-2 variants of concern.

More specifically, albeit high levels of antibodies were demonstrated to the RBD specific for the wild type virus, the titers for UK strain (B.1.1.7) and South African strain (B.1.351) were lower in previously naïve health care workers. Furthermore, ex vivo T cell responses were found to S1 in 63.9% and S2 in 31.9% of health care workers.

The ACE2 blocking titers (as measured by the SARS-CoV-2 surrogate virus neutralization test) substantially increased from a median of 54.1 to 97.9% of inhibition in previously infected health care workers. Finally, antibodies to the RBD for the UK and South African variants also rose significantly.

Superb immunogenicity of a single dose

In short, a single dose of the Oxford–AstraZeneca COVID-19 vaccine was shown to be very immunogenic in previously naïve individuals and able to induce antibody levels that exceed those following a mild or asymptomatic natural infection.

“Our results suggest a single dose of vaccine based on the original sequence may still induce a significant increase in antibodies cross-reactive with the variants of concern – perhaps sufficient to ameliorate disease”, say the authors of this study.

“It would be important to find out if these individuals who had a poor serological response to the vaccine would be more susceptible to infection in future in prospective studies,” they further caution in this medRxiv paper.

As many countries worldwide have a partially immunized population, with only a single vaccine dose administered, studies like these leave us with very important data and may tailor our future vaccination and public health approaches.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.