key: cord-0279056-k9u7ewze
authors: Lien, C. E.; Lin, Y.-J.; Lin, Y.-L.; Tai, I.-C.; Chen, C.
title: The age-dependent immunogenicity after two doses of MVC-COV1901 vaccine.
date: 2021-12-14
journal: nan
DOI: 10.1101/2021.12.12.21267573
sha: c4f343864c32bddf0d4f00bd719461b5b5e3bce6
doc_id: 279056
cord_uid: k9u7ewze

A post-hoc analysis of the phase 2 data was performed for the SARS-COV-2 subunit protein vaccine MVC-COV1901. Anti-spike IgG, neutralization assays with live virus and pseudovirus were used to demonstrate age-dependent vaccine-induced antibody response to the vaccine. Results showed that an association exists between age and immune responses to the vaccine, providing further support for the need of booster shots, especially for the older age groups.

MVC-COV1901 is a protein subunit COVID-19 vaccine using the prefusion stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide [1] . MVC-COV1901 has shown favorable safety profile and robust immunogenicity in the phase 2 clinical trial, and has been approved for use in Taiwan since August 2021 [1] . However, how age impacts the immunogenicity elicited by MVC-COV1901 was unknown. In this study, we described the association between age and the antibody titers in 903 healthy adults from 20 to 87 years of age 28 days after the first or second dose in a post-hoc analysis of our phase 2 study.

The age-dependent immunogenicity elicited by MVC-COV1901 was observed from the results of three assays, live-virus SARS-CoV-2 neutralization assay, pseudovirus neutralization assay, and the binding of antibodies against SARS-CoV-2 spike. All of the assays followed the same protocols as in the original phase 2 study [1] . Associations between age and NT50 for the Wuhan ancestral strain and the variants were determined by linear regression in Graphpad Prism 8.0.

The live-virus neutralization assay showed a trend of decreasing immune responses to the vaccine as age increases (Fig 1A) . The youngest group of participants (20-29 years; N=188) had a GMT of 914.7 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.12.21267573 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

(95% CI, 834.5 to 1002.5), compared to the oldest group (80-87 years; N=7) which has a GMT level of 315.4 (95% CI, 225.1 to 441.9). This is a 65.5% reduction (P<0.001) in GMT. The binding antibody titers also differed in an age-dependent manner. At 28 days after the first dose, the youngest group of participants (20-29 years; N=188) had a GMT of 748.0 (95% CI, 645.8 to 866.5), and the oldest group reduction (P=0.0024) (Fig 1B) . The age-dependent association appears to be independent of the strain, as neutralization against pseudovirus expressing spike protein of the Wuhan ancestral strain, Alpha, and Gamma variants SARS-CoV2 all showed a similar trend (Fig 2) .

The finding of our post-hoc analysis suggests that protection by the vaccine against SARS-CoV-2 infections is age-dependent since neutralizing antibody levels correlated with age [2] . This is consistent with observations reported by others, that an increase in breakthrough COVID infections was found among older adults [3] . The effect of the age-dependent decrease in immune response appears to be less after the second dose, supporting the positive impact of booster vaccines for older adults. Lastly, the agedependent decrease in immune response is independent of the virus strains, as similar trends were observed in the ancestral strain, Alpha, and Gamma variants. These reports strengthen the notion that older adults have a lower immune response than younger adults. Second and possibly third dose will likely be important for older adults.

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.12.21267573 doi: medRxiv preprint

Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan. The Lancet Respiratory Medicine

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study. The Lancet Infectious Diseases

. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprintThe copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.12.21267573 doi: medRxiv preprint