Vaccine-induced neutralizing antibodies against SARS-CoV-2 Omicron variant isolated in Osaka, Japan

  1. Satoshi Hiroi
  2. Saeko Morikawa
  3. Kazushi Motomura
  4. Haruyo Mori

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Abstract

To study vaccine-induced neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants isolated in Osaka, Japan, microneutralization tests were performed on serum samples from 32subjects who received a second dose of vaccination, and 10 of those who received the third dose of vaccination. Geometric mean titres (GMTs) for the D614G strain, Alpha variant, Delta variant, and Omicron BA.1 of the subjects after the second dose of vaccination were 19.5, 21.8, 6.3 and 2.0, respectively. The GMT for the Delta variant was significantly lower than that for the D614G strain and Alpha variant, and the GMT for the Omicron BA.1 was significantly lower than that for the Delta variant. Among the subjects who received three doses of vaccination, the GMTs for the Omicron BA.1 (62.8) and BA.2 (38.6) were significantly higher than that for the Omicron BA.1 after the second dose. Thus, in the present study, the second dose of vaccination induced neutralizing antibodies against SARS-CoV-2 strains, and the reactivity of neutralizing antibodies to the variants was thought to be enhanced by the third dose of vaccination. The serum samples used in this study will be useful in evaluating the reactivity of vaccine-induced antibodies to newly emerging variants.

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  1. Version published to 10.1099/acmi.0.000465.v3 on Access Microbiology
  2. Version published to 10.1099/acmi.0.000465.v2 on Access Microbiology
  3. Access Microbiology

    Thank you for addressing the reviewers comments and adding in the table detailing the spike protein mutations of each variant. This manuscript is now suitable for publication, with one caveat- all raw data including technical replicates need to be provided as part of our open data policy. The table you have provided as a supplementary S1. only gives a single average data point for each sample. The materials and methods state each sample was assessed in duplicate. Therefore, please deposit all raw data underlying the work in the Society’s data repository Figshare account here: https://microbiology.figshare.com/submit. Please also cite this data in the materials and methods of the main manuscript and list it as a unique reference in the References section. When you resubmit your article, the Editorial staff will post this data publicly on Figshare and add the DOI to the Data Summary section where you have cited it. This data will be viewable on the Figshare website with a link to the manuscript and vice versa, allowing for greater discovery of your work, and the unique DOI of the data means it can be cited independently should it be used by other researchers.

  4. Access Microbiology

    I would like to thank both reviewers for their giving their time and expertise to assess this manuscript- it is appreciated. Thank you also to the authors for patiently waiting for this manuscript to be moved through the peer review system, which I acknowledge has taken considerable time. Both reviewers have commented that the methodology is sound and that the conclusions are supported by the data. Whilst I acknowledge the comments of reviewer 1 about the size and scope of the study and the limitations this places on the data, Access Microbiology operates a sound science policy with methodological rigour outweighing impact and novelty. Therefore, my decision is for minor amendments to be made to improve the manuscript before it can be accepted for publication. Can the authors please make the amendments suggested by reviewer 2. The addition of a figure or table outlining the differences in the spike gene between variants would certainly improve the manuscript. In line with Access Microbiology’s Open Data policy authors also need to deposit all of the raw data analysed in this study into an open access repository, or include it as a supplementary table in the manuscript so that it can be accessed by other researchers. https://www.microbiologyresearch.org/open-data

  5. Access Microbiology

    Comments to Author

    This study intends to investigate the vaccine-induced neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants isolated in Osaka, Japan. Microneutralization tests were performed on serum samples from 32 subjects who received two doses of vaccination and 10 subjects with three doses. Among those with two doses, the Geometric Mean Titres (GMT) for the Delta variant was significantly lower than that for the D614G strain and Alpha variant, and the GMT for the Omicron BA.1 was significantly lower than that for the Delta variant. Among those with three doses, the GMTs for the Omicron BA.1 and BA.2 were significantly higher than that for the Omicron BA.1 in those with two doses. Several suggestions: 1. Line 68, [encoding the SARS-CoV-2 full-length spike] is suggested to be added after [BNT162b2 mRNA vaccine]. 2. Please add a figure or table to outline the differences of various SARS-CoV-2 variants [including the vaccine strain] in the spike gene. Alternatively, cite a reference to mention the differences of these variants in the spike gene. 3. Lines 101, 102, 106, please write down the p values to show they are not statistically important. 4. In this study, antibody titers of two different groups [with two doses, with three doses] were compared. Please compare these two groups, is there any difference in main demographic characteristics, such as gender, age, etc.

    Please rate the manuscript for methodological rigour

    Very good

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  6. Access Microbiology

    Comments to Author

    This paper is a limited study of 32 subjects vaccinated twice with the commercial COVID vaccines and 10/32 that received a second booster. The goal was to determine the neutralizing antibody response to four variants of SARS CoV2. The results indicate that the vaccinates did respond to all four variants with the initial vaccination and subsequent booster, but the level of response varied depending on the isolate of SARS CoV 2 used as the target in the neutralization assay. The results are presented well. The methodology, results and conclusions agree. The sample size of this paper is very limited and the study only evaluated the neutralization antibody response. There was no attempt to measure the overall antibody response or to examine cell mediated immunity. Realize that this was not the purpose of the study but a large sample size, more frequent sampling of the subjects and more expanded analysis of the immune response would have been a stronger paper.

    Please rate the manuscript for methodological rigour

    Good

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Strongly support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  7. Version published to 10.1099/acmi.0.000465.v1 on Access Microbiology