four doses of the inactivated sars cov 2 vaccine redistribute humoral immune responses CORD-Papers-2022-06-02 (Version 1)

Title: Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain
Abstract: A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs) 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a turning point. The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.
Published: 2022-02-21
DOI: 10.1101/2022.02.19.22271215
DOI_URL: http://doi.org/10.1101/2022.02.19.22271215
Author Name: Wang J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_j
Author Name: Deng C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/deng_c
Author Name: Liu M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_m
Author Name: Liu Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Li L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_l
Author Name: Huang Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/huang_z
Author Name: Shang L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/shang_l
Author Name: Jiang J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jiang_j
Author Name: Li Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_y
Author Name: Mo R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mo_r
Author Name: Zhang H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_h
Author Name: Peng S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/peng_s
Author Name: Xiao H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xiao_h
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: https://doi.org/10.1101/2022.02.19.22271215 http://medrxiv.org/cgi/content/short/2022.02.19.22271215v1?rss=1
has_full_text: FALSE
G_ID: four_doses_of_the_inactivated_sars_cov_2_vaccine_redistribute_humoral_immune_responses