Immunogenicity of virus-like particle vaccine candidates against SARS-CoV-2 infection

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Abstract

SARS-CoV-2 variants could become more virulent and transmissible due primarily to the mutations of the viral spike protein, rendering currently approved vaccines less effective. More effective vaccines are needed as vaccination is by far the best strategy against this virus. We have produced two SARS-CoV-2 virus-like particles (VLPs) using a baculovirus BacMam expression platform and examined their immunogenicity in mice. VLP1 contains the spike protein from the Wuhan strain whereas VLP2 contains that of an Omicron variant. Mice immunized with VLP1 and boosted with VLP2 developed significantly higher antibodies in the sera, and more IFNγ secreting cells than the control group. Furthermore, both VLPs induced virus neutralization antibodies against the ancestral Wuhan and an Omicron variant. In conclusion, our study warrants further development of VLPs as effective vaccines against emerging variants of SARS-CoV-2.

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  1. I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. The work presented is clear and the arguments well formed. The manuscript is well written and contributes to the literature. Thank you for addressing all reviewers comments satisfactorily and in a timely manner.

  2. Thank you for submitting your manuscript for publication in Access Microbiology. It has been examined by expert reviewers who have concluded that the work is of potential interest to the readership of Access Microbiology. However, based on the comments received, it is clear that a major revision of this manuscript will be required before a decision can be made on its publication. I will be pleased to consider a revised manuscript along with a document including a point by point response to each of the reviewers comments. Your revised manuscript may be returned to one or more of the original reviewers, along with your itemised response to the reviewers’ comments. You may wish to have your article edited before you submit the revision. This is not compulsory but it may help reviewers to fully understand your article. Many language-editing services are available, but we have partnered with Editage to provide publication-focused editing services to our authors at a 15% discount. To take advantage of this offer visit our Editage page (https://www.editage.com/microbiologyresearch/). Please note that language editing does not guarantee that your article will be accepted for publication. If you have used a language editing service when preparing or revising your manuscript, please include this within your acknowledgement section. This statement should indicate the type of editing undertaken and the name of the service used.

  3. Comments to Author

    The manuscript describes the development of virus like particle (VLP)-based vaccine for SARS-CoV-2. The data presented is straightforward approach of characterization of the vaccine and in vivo immunogenicity in mice. there are few words that seem to be not suitable, e.g. classified by centrifugation, canned with Odyssey etc., 0.002 M EDTA acid disodium salt dehydrate) -delete acid mention pH wherever you use buffer D10 medium: expand it measured ELISPOT- missing a word looks like some prior publications of VLP vaccines are not cited.

    Please rate the manuscript for methodological rigour

    Very good

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

    Very 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

  4. Comments to Author

    Reviewer Comments to Author box. Please include specific and constructive comments on each of the following criteria: 1. Methodological rigour, reproducibility and availability of underlying data It would be very helpful to label the size of bands in the Western blot in figure 1B. Because the VLP systems were generated for vaccine/immunizations, it would be helpful to directly link the sequences of the plasmid and inserts used somewhere in the paper. The authors should expand on quantity of VLPs obtained from both Wuhan and Omicron preparations. How long were VLPs stored after preparation before going into animal injections? How were they stored? On page 10, line 202: what do authors mean mice immunized with VLPs only produced significantly higher Omicrson S1 specific? They must mean the VLP1 followed by VLP2 as it is the only way VLPs were done from the methods and results included. Comparing VLP1 followed by VLP2 to just VLP2 would be helpful in broad knowledge. How robust was luciferase signal in figure 3 for PBS and pseudovirus experiments? It is challenging to tell with the data as presented. What type of statistical analysis was done for figures 2 and 3. 2. Presentation of results The results are of mild significance since they examine VLP1 (WT) and VLP2 (omicron) ability to stimulate mice to generate antibodies. It would be helpful to compare VLP1 to VLP2 to better see how WT vs Omicron antibodies develop. The results could be expanded in a more detail as it stands at less than 2 pages double spaced. Not a lot more needed but some more writing to explain what was done/interpreted would help in several places. 3. How the style and organization of the paper communicates and represents key findings The organization is fine. 4. Literature analysis or discussion No issues 5. Any other relevant comments The writing and grammar should improve and could benefit from an editing/writing consultant.

    Please rate the manuscript for methodological rigour

    Satisfactory

    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