key: cord-0938220-gaohm9wk
authors: Lien, C.-E.; Kuo, T.-Y.; Lin, Y.-J.; Lian, W.-C.; Lin, M.-Y.; Liu, L. T. C.; Chou, Y.-C.; Chen, C.
title: Evaluating the neutralizing ability of a CpG-adjuvanted S-2P subunit vaccine against SARS-CoV-2 Variants of Concern
date: 2021-03-22
journal: nan
DOI: 10.1101/2021.03.19.21254000
sha: 5873f913d344b48bc94dd74e82664f4f5bffea48
doc_id: 938220
cord_uid: gaohm9wk

Vaccination is currently the best weapon to control the COVID-19 pandemic. However, an alarming number of novel variants termed Variants of Concern (VoC) were found to harbor mutations that diminished the neutralizing capacity of antibodies elicited by the vaccines. We have investigated the neutralizing titers of antibodies from sera of humans and rats immunized with the MVC-COV1901 vaccine against pseudoviruses coated with the wildtype, D614G, B.1.1.7, or B.1.351 spike proteins. Rats vaccinated with two doses of adjuvanted S-2P retained neutralization activities against the B.1.351 variant, albeit with a slight reduction compared to wildtype. Phase 1 vaccinated subjects showed more reduced neutralization abilities against the B.1.351 variant. The study is among the first, to our knowledge, to demonstrate dose-dependent neutralizing responses against VoCs, particularly against B.1.351, from different doses of antigen in a clinical trial for a subunit protein COVID-19 vaccine. The appearance of vaccine escape variants is a growing concern facing many current COVID-19 vaccines and therapeutics. Strategies should be adopted against the ever-changing nature of these variants. The observations of this study grant us valuable insight into preemptive strikes against current and future variants.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 22, 2021. ; https://doi.org/10.1101/2021.03.19.21254000 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 60 mutation alone rendering the protein refractory to antibody binding via steric hindrance 6 . The industry has 61 scrambled for strategies to combat these emerging variants, including redesigning the vaccine to elicit either 62 variant-specific or more broadly neutralizing antibodies or administering the additional dose to boost the 63 immune response to compensate for the reduction in neutralization 9-11 .

Medigen's MVC-COV1901 is a SARS-CoV-2 vaccine consisting of recombinant prefusion stabilized 65 spike protein S-2P with CpG 1018 and aluminum hydroxide (alum) adjuvants which have been shown to 66 induce a very high level of antibody titers in preclinical studies 12 . We sought to ask whether MVC-COV1901 67 could still defend against these variants with its ability to induce a high level of immunogenicity. We found 68 that antisera taken from the phase 1 vaccinated subjects showed neutralization against the wildtype, D614G, 69 and B.1.1.7 pseudoviruses, while B.1.351 pseudoviruses could be neutralized but to a lesser extent. It was also 70 found that a higher antigen dose elicited better neutralizing antibody response. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

We took rat sera from previous toxicology studies to assess antibodies' neutralization ability against 75 emerging variants and subjected them to wildtype and B.1.351 pseudovirus neutralization assays. As shown in 76 Figure 1 , the antibodies were still effective against the B.1.351, although the titers were reduced by 1.49 to 4.6-77 fold in ID50 and 1.4 to 3.05-fold in ID90 relative to wildtype. The overall trend is that with the increase of the is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

In this study, we showed that in humans, two injections of a subunit vaccine consisting of the prefusion is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 22, 2021. ; https://doi.org/10.1101/2021.03.19.21254000 doi: medRxiv preprint effective mAbs against the viral variant in question ( Fig. 1 and 2) . Our findings suggest that the neutralizing 

Developing a new COVID-19 vaccine to cope with the VoC is inherently reactive due to the following 135 unknowns, the clinical significance of the emerging strain, the geographical distribution where the strain will 136 be predominant, and how they will mutate further. The FDA has published guidance for the industry to change 137 the antigen based on the VoC to gain regulatory approval using the data accrued from the earlier development is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

Our study's limitation is that the sera were taken four weeks after the second shot of MVC-COV19 when 156 the immunity has peaked and starting to wane. Therefore, we could not evaluate the impact of waning immunity 

All procedures in this study involving animals were conducted to avoid or minimize discomfort, distress, is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

way ANOVA with Tukey's multiple comparison test was used to calculate significance. * = p < 0.05, ** = p < 320 0.01, *** = p < 0.001, **** = p < 0.0001.

. CC-BY-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 22, 2021. ; https://doi.org/10.1101/2021.03.19.21254000 doi: medRxiv preprint

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