Hybrid immunity from mRNA vaccines and breakthrough Omicron infections induces stronger immune responses against Omicron BQ.1.1

In a recent study posted to the medRxiv* preprint server, researchers evaluated plasma samples from individuals vaccinated with a fourth booster dose of mono- or bivalent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine to evaluate the recognition and neutralization capacity against the ancestral (D614G) strain and the Omicron BQ.1.1 subvariant.

Study: Humoral responses against BQ.1.1 elicited after breakthrough infection and SARS-CoV-2 mRNA vaccination. Image Credit: CROCOTHERY/Shutterstock
Study: Humoral responses against BQ.1.1 elicited after breakthrough infection and SARS-CoV-2 mRNA vaccination. Image Credit: CROCOTHERY/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

Background

The emergent Omicron subvariants with mutations in the spike glycoprotein region challenge the immunity induced by early coronavirus disease 2019 (COVID-19) vaccines. The newly emergent Omicron subvariant BQ.1.1 has shown resistance against the humoral immunity elicited by the monovalent mRNA vaccine and is now one of the major circulating SARS-CoV-2 variants in many countries. The BQ.1.1 subvariant carries five convergent mutations in the receptor binding domain that enhance its ability to escape vaccine-induced immunity.

Health authorities in various countries have now approved the use of bivalent mRNA vaccines, such as those developed by Pfizer and Moderna, which encode the spike proteins of the ancestral SARS-CoV-2 strain and an Omicron subvariant. Furthermore, studies have provided evidence that hybrid immunity, induced by vaccinations and previous SARS-CoV-2 infections, provides better protection against severe infections than vaccine-induced immunity alone.

Furthermore, the waning of vaccine-induced immunity and the emergence of immune-evading Omicron infections has led to an increase in breakthrough infections. Investigating the neutralizing capacity of plasma samples from individuals with vaccinations and breakthrough infections will help understand the protection offered by hybrid immunity against emergent Omicron subvariants such as BQ.1.1.

About the study

In the present study, plasma samples were collected from 63 individuals vaccinated with three doses of the monovalent Pfizer mRNA vaccine and the fourth dose of either the Pfizer or Moderna monovalent mRNA vaccines or the Pfizer or Moderna bivalent vaccines containing BA.4/BA.5 or BA.1 spike protein mRNAs, respectively.

Of the 63 individuals, 20 had confirmed breakthrough Omicron infections with increased anti-nucleocapsid antibodies between the fourth week and fourth month after the third dose or between four months after the third dose and four weeks after the fourth dose of the vaccine. While the remaining 43 individuals might have had previous SARS-CoV-2 infections, no significant increase in anti-nucleocapsid antibodies was detected in their serum samples.

Enzyme-linked immunosorbent assay (ELISA) was used to detect the anti-nucleocapsid immunoglobulin levels in all plasma samples. Human embryonic kidney (HEK) 293T cells transfected with a green fluorescent protein expressor and full-length spikes of SARS-CoV-2 were used for the flow cytometry analysis to detect the recognition of the ancestral and BQ.1.1 spikes by the plasma. Additionally, HEK 293T cells expressing angiotensin-converting enzyme-2 (ACE-2) and lentiviral vectors with plasmids encoding spike proteins of the ancestral D614G strain and the Omicron BQ.1.1 subvariant were used for the virus-neutralization assay. The neutralization at the half-maximal inhibitory concentration (IC50) was calculated for the plasma samples.

Results

The results indicated no significant difference in recognition of the ancestral D614G strain spike protein four weeks and four months after the third mRNA vaccine dose between individuals with and without breakthrough infections. However, compared to individuals without breakthrough Omicron infections, individuals with breakthrough infections showed better recognition of the D614G strain spike protein after the fourth vaccine dose, irrespective of the type of vaccine.

In contrast, individuals with breakthrough infections showed better recognition of the Omicron BQ.1.1 spike protein at four months after the third vaccine dose than those who did not have previous Omicron infections. This difference in BQ.1.1 spike protein recognition was more pronounced four weeks after the fourth vaccine dose. However, the level of spike protein recognition was lower for the BQ.1.1 subvariant than that of the D614G strain.

Four weeks and four months after the third dose, no significant differences were detected in the neutralizing ability of the plasma samples from individuals with and without breakthrough Omicron infections. However, after the fourth vaccine dose, individuals with breakthrough infections developed significantly higher neutralizing antibodies against the ancestral D614G strain and the BQ.1.1 subvariant at four weeks than individuals without breakthrough infections.

All individuals with breakthrough Omicron infections developed neutralizing antibodies against the BQ.1.1 spike protein after the fourth vaccine dose. However, even after the fourth vaccine dose, the neutralization of the BQ.1.1 spike was lower than that of the D614G spike protein. While the results suggested that the Moderna bivalent mRNA vaccine induced better recognition and neutralization of BQ.1.1 spike protein than the Pfizer bivalent vaccine, the results were insignificant.

Conclusions

Overall, the results reported that hybrid immunity induced by breakthrough SARS-CoV-2 Omicron infections and four doses of the mono- or bivalent mRNA vaccine resulted in increased recognition and neutralization of the emergent Omicron BQ.1.1 subvariant.

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:
  • Preliminary scientific report. Alexandra Tauzin, Mehdi Benlarbi, Halima Medjahed, Yves Gregoire, Josee Perreault, Gabrielle Gendron-Lepage, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Cecile Tremblay, Daniel E Kaufmann, Valerie Martel-Laferriere, Ines Levade, Marceline Cote, Gaston De Serres, Renee Bazin, and Andres Finzi. (2022). Humoral responses against BQ.1.1 elicited after breakthrough infection and SARS-CoV-2 mRNA vaccination. medRxiv. doi: https://doi.org/10.1101/2022.12.20.22283723 https://www.medrxiv.org/content/10.1101/2022.12.20.22283723v1
  • Peer reviewed and published scientific report. Tauzin, Alexandra, Mehdi Benlarbi, Halima Medjahed, Yves Grégoire, Josée Perreault, Gabrielle Gendron-Lepage, Laurie Gokool, et al. 2023. “Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 MRNA Vaccination.” Vaccines 11 (2): 242. doi.org/10.3390/vaccines11020242https://www.mdpi.com/2076-393X/11/2/242

Article Revisions

  • Mar 14 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.
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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Comments

  1. Intentional Insight Intentional Insight United States says:

    Where are the studies on natural immunity? Why is this population being ignored?

    • Michael Gallagher Michael Gallagher Canada says:

      The medical communities refusal to compare antibodies & protection from Natural Immunity ONLY isunforgivable! Their refusal to do that simple additional analysis, which they have data for, is a major deficiency that fuels distrust of these studies.

  2. jetsom1000 jetsom1000 United States says:

    glad there was a conclsion.....so getting sick and boosters is the best defense. getting these shots and flu shots shingles etc. cant be good in the long term..but the older you get the higher the risks

  3. Steven Brown Steven Brown Australia says:

    Couldn't it be that the actual I fiction was the only significant factor?

  4. Jasmine SkyDancer Jasmine SkyDancer United States says:

    Jetsom1000 summarized my thoughts perfectly after reading the well written by Dr. Sidharthan; load up on the mRNA vaccine and once you catch the SARS variant you'll have the desired immunity to (HOPEFULLY) keep from getting very sick (!).  For the elderly, that may mean a couple of weeks in the hospital from being very ill from the variant. I'm stating this example because I know an elder was fully vaccinated w/the variant booster and just endured the hospital stay. Of course, the elder was happy to be home before Christmas and believes if they didn't have their shots they would've had a worse outcome.
    I also know another elder who taught math at a university who refuses the vaccine and believes the variants are from individuals that are vaccinated; the virus mutates much more rapidly than flu. The math elder is well but remains mostly at home. I'm vaccinated (J&J and Pfizer boosters) but not with the most recent variant booster.  From the prior examples, I'm darned if I get the booster or not - without getting infected w/variant SARS my immunity won't be 'up to par'.  

    How about determining ones immunity level first before getting future boosters?  Of course healthy individuals, immune compromised / chronic illness individuals and elderly (healthy or not) may have differing levels, but once the immunity level is determined, then the patient can get a booster. Patient wise and cost wise (considering the 'cold chain cost' of mRNA vaccines - our only option for reasons known only by the vaccine makers of course and the CDC, FDA and current administration!) it might help reduce the variants being created help with gaining public trust than just telling us we should get boosters as soon as they are on the market - that is averaging 2 shots a year.

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