Combined COVID-19 vaccination regimen found to induce more potent anti-SARS-CoV-2 antibodies

NewsGuard 100/100 Score

In a recent study posted to the bioRxiv* preprint server, researchers assessed vaccine-induced humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) post four different vaccination regimens comprising homologous and heterologous vaccine doses.

Study: Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens. Image Credit: Sutthituch/Shutterstock
Study: Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens. Image Credit: Sutthituch/Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

The coronavirus disease 2019 (COVID-19) pandemic has led to multinational efforts for SARS-CoV-2 vaccine development at a rapid pace which has resulted in diverse vaccination modalities, immunogenic combinations, and dose intervals for the existing SARS-CoV-2 vaccines.

About the study

In the present study, researchers compared the anti-SARS CoV-2 receptor-binding domain (RBD) immunoglobulin (IgG, IgA, and IgM) titers induced by double mRNA vaccination, double ChAdOx1 vaccination, single Ad26.COV2.S vaccination, or heterologous ChAdOx1 and mRNA vaccination.

Healthcare workers without prior COVID-19 history were grouped into four cohorts based on the vaccination regimens. The participants’ sera were collected one month and six months after the first vaccination. In addition, sera were collected one month after the second mRNA vaccination.

The neutralization potency of serum anti-SARS-CoV-2 RBD IgG titers was assessed using enzyme-linked immunosorbent assays (ELISA) whereas the breadth of SARS-CoV-2 Wuhan-Hu-1/wild-type (WT), Delta, and Omicron BA.1 neutralization was evaluated using human immunodeficiency virus-1 (HIV-1) pseudotyped with the corresponding SARS-CoV-2 strain spike (S) protein RBD, respectively.

Memory B lymphocytes expressing receptors binding to the SARS-CoV-2 S N-terminal domain (NTD) and RBD were analyzed to assess memory B lymphocyte development following vaccination. Further, the genes of Wuhan-Hu-1 RBD-specific B lymphocytes were sequenced and recombinant antibodies were produced in vitro to assess the SARS-CoV-2 specificity and neutralization after six months of the prime vaccination.

In addition, biolayer interferometry (BLI) analysis was performed to assess the binding affinities and to define the epitopes recognized by the vaccine-induced memory antibodies. Further, the structure or Wuhan-Hu-1 SARS-CoV-2 S bound to the AZ090 antibody was examined by cryo-electron microscopy (cryo-EM).

Results

After one month of prime AZ/AZ or AZ/BNT vaccination, the RBD-binding memory B lymphocyte count was substantially lower than that after Ad26.COV2.S and mRNA vaccination. However, the count improved after AZ/AZ or AZ/BNT boosts although the count was still lower than that observed after double mRNA vaccination. Contrastingly, the NTD-binding memory B lymphocyte count remained unaltered after the AZ/AZ or AZ/BNT boosts and was comparable to that induced by double mRNA vaccination but substantially lower than that by Ad26.COV2.S vaccination.

After four months of prime AZ/BNT vaccination, Delta and Omicron BA.1 neutralization titers were 5.5-fold and 11.6-fold lower than those against WT, respectively. The corresponding titers further decreased by 5.6-fold and 13.6-fold after six months of vaccination, respectively. In comparison, after four months of AZ/AZ prime vaccination, the corresponding titers decreased by 5.8-fold and 21-fold, respectively. Delta neutralization titers further decreased by 6.4-fold after six months of prime vaccination whereas Omicron BA.1 neutralization decreased slightly. Of note, the antibody titers among AZ/BNT vaccinees negatively correlated with the interval between the prime and boost doses, indicating increased COVID-19 protection by decreasing dosing intervals. 

After six months of prime vaccination, AZ/BNT vaccinees demonstrated substantially higher SARS-CoV-2 WT neutralization compared to the AZ/AZ vaccinees and similar neutralization as the mRNA vaccinees. Ad26.COV2.S vaccinees demonstrated the least SARS-CoV-2 WT neutralization while AZ/AZ and AZ/BNT vaccinees demonstrated comparable IgA and IgM titers.

After a month of the second vaccination, mRNA and ChAdOx1 boosters increased the IgG titers by 2.6-fold and 12-fold among AZ/AZ and AZ/BNT vaccinees, respectively. The corresponding titers decreased by 1.5-fold and 3.2-fold after four to six months of vaccination, respectively. However, the titers remained substantially high among AZ/BNT vaccinees even after six months of prime vaccination. Notably, the second vaccination escalated the mean half-maximal neutralizing titers (NT50) among AZ/AZ vaccinees and AZ/BNT vaccinees from 139 to 305 and 1946, respectively.

A month after the vaccine boost, Omicron BA.1 neutralization by AZ/BNT vaccinees exceeded those by AZ/AZ and mRNA vaccinees by 6.4-fold and 10.3-fold, respectively. Omicron BA.1 neutralizing titers among AZ/BNT vaccinees remained higher even after six months of prime vaccination, whereas the neutralizing titers among Ad26.COV2.S vaccine recipients were much lower.

Clonal expansion of RBD-specific B lymphocytes after six months of prime vaccination represented 13%, 22%, 16%, and 23% of the memory B lymphocytes among Ad26.COV2.S, AZ/BNT, AZ/AZ, and mRNA vaccines, respectively. The VH3-53, VH3-30, and VH1-46 genes were highly expressed among AZ/AZ and AZ/BNT vaccinees. No differences were observed in the somatic mutations among AZ/AZ and AZ/BNT vaccinees. However, more mutations were noted in Ad26.COV2.S and mRNA vaccinees.

The mean half-maximal concentrations (EC50) of RBD-binding antibodies elicited by AZ/AZ vaccinees and AZ/BNT vaccines were similar. The binding affinities of antibodies induced by the mRNA, Ad26.COV2.S, AZ/AZ or AZ/BNT vaccines were also similar. However, the epitopes distributed in the memory antibody repertoires significantly differed between the vaccination regimens. The structural analyses showed that the AZ090 binding orientation was similar to that of previously described antibodies which were isolated after natural SARS-CoV-2 infection.

Overall, the study findings showed superior humoral immunity induced by heterologous AZ/BNT vaccination against SARS-CoV-2 strains. All vaccines were effective, although vaccine efficacy waned with time and could be enhanced by decreasing the interval between the prime and boost doses.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • May 13 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Toshniwal Paharia, Pooja Toshniwal Paharia. (2023, May 13). Combined COVID-19 vaccination regimen found to induce more potent anti-SARS-CoV-2 antibodies. News-Medical. Retrieved on June 13, 2024 from https://www.news-medical.net/news/20220518/Combined-COVID-19-vaccination-regimen-found-to-induce-more-potent-anti-SARS-CoV-2-antibodies.aspx.

  • MLA

    Toshniwal Paharia, Pooja Toshniwal Paharia. "Combined COVID-19 vaccination regimen found to induce more potent anti-SARS-CoV-2 antibodies". News-Medical. 13 June 2024. <https://www.news-medical.net/news/20220518/Combined-COVID-19-vaccination-regimen-found-to-induce-more-potent-anti-SARS-CoV-2-antibodies.aspx>.

  • Chicago

    Toshniwal Paharia, Pooja Toshniwal Paharia. "Combined COVID-19 vaccination regimen found to induce more potent anti-SARS-CoV-2 antibodies". News-Medical. https://www.news-medical.net/news/20220518/Combined-COVID-19-vaccination-regimen-found-to-induce-more-potent-anti-SARS-CoV-2-antibodies.aspx. (accessed June 13, 2024).

  • Harvard

    Toshniwal Paharia, Pooja Toshniwal Paharia. 2023. Combined COVID-19 vaccination regimen found to induce more potent anti-SARS-CoV-2 antibodies. News-Medical, viewed 13 June 2024, https://www.news-medical.net/news/20220518/Combined-COVID-19-vaccination-regimen-found-to-induce-more-potent-anti-SARS-CoV-2-antibodies.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
IgG from long COVID patients induces specific symptoms in mice, confirming autoimmunity's role