key: cord-0730293-hzjcjn1m authors: Huang, Qingrui; Zeng, Jiawei; Lang, Qingyun; Gao, Feng; Liu, Dejun; Tian, Siyu; Shi, Rui; Luo, Ling; Wang, Hao; Hu, Liping; Jiang, Linrui; Liu, Yawei; Li, Kailiang; Wu, Yunbo; Xu, Junjie; Jiang, Wenxi; Guo, Ning; Chen, Zhihai; Hao, Xiaohua; Jin, Ronghua; Yan, Jinghua; Sun, Yufa title: Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine date: 2022-01-27 journal: bioRxiv DOI: 10.1101/2022.01.25.476850 sha: 94584575ba41d59419b5e40d2a7ac1efd84bda5d doc_id: 730293 cord_uid: hzjcjn1m Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant. the fifth variant of concern (VOC) and named it Omicron (5, 6 (Table S1 ). For all of the serum specimens, the binding antibody titers 82 were 5-15 times lower for the Omicron than variant for the prototype strain (Fig. 1A) . 83 Notably, except for one specimen from an individual receiving PRV vaccinations (Table S1 ). Binding, blocking and neutralizing 108 antibodies titers in all of the groups were markedly higher against the prototype strain 109 than against the Omicron variant (Fig. 2) . The booster dose with IAV, PRV, and AdV blocking antibodies against the prototype were detected in those mice (Fig. 4B-D) . 152 The mice immunized with all types of booster shots had significantly elevated anti-153 prototype strain binding, blocking, and neutralizing antibody titers, as well as anti- 154 Omicron binding and neutralizing antibody titers (Fig. 4B-D) . In addition, all of the 155 booster groups induced significantly higher anti-Beta and anti-Delta binding antibody 156 titers compared with the no-booster control group (Fig. S5-6) . However, only mice 157 immunized with Delta and Omicron boosters developed significantly higher anti-158 Omicron blocking antibody titers compared with no booster control (Fig. 4C) . 159 Notably, the prototype, Beta, Delta, Beta-Delta and Omicron vaccine boosters elicited 160 Omicron-neutralizing NT50 titers with values of 423, 1,202, 3,073, 1,548, and 7,710, 161 respectively, and only those elicited by Omicron booster were significantly higher 162 than those by the prototype booster (Fig. 4D) , suggesting that Omicron-based mRNA 163 vaccine booster is superior to prototype-based mRNA vaccine booster in elevating 164 Omicron-neutralizing immunity. Pseudovirus neutralization titers, expressed as 50% neutralization dilutions (NT50). 244 The pseudoviruses used in the study included wild-type strain and Omicron. The Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift A single-dose mRNA vaccine provides a long-term protection 284 for hACE2 transgenic mice from SARS-CoV-2 Antibody-mediated broad sarbecovirus neutralization through 287 ACE2 molecular mimicry A human neutralizing antibody targets the receptor-binding site of 289 SARS-CoV-2 Striking Antibody Evasion Manifested by the Omicron Variant of 291 SARS-CoV-2 Considerable escape of SARS-CoV-2 Omicron to antibody 293 neutralization Efficacy and safety of an inactivated whole-virion SARS-295 CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, 296 placebo-controlled, phase 3 trial in Turkey Safety and immunogenicity of an inactivated COVID-19 vaccine Safety and immunogenicity of a recombinant tandem-repeat 12 Humoral immunogenicity and reactogenicity of CoronaVac or 312 ZF2001 booster after two doses of inactivated vaccine Safety, reactogenicity, and immunogenicity of homologous 315 and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and 316 BNT162b2: a prospective cohort study. The Lancet. Respiratory medicine 9 Recombinant protein subunit vaccine booster following two-dose 319 inactivated vaccines dramatically enhanced anti-RBD responses and 320 neutralizing titers against SARS-CoV-2 and Variants of Concern Reduced neutralisation of SARS-CoV-2 omicron 1.1.529 variant by post-immunisation serum SARS-CoV-2 Omicron has extensive but incomplete escape of 326 Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. 327 medRxiv Omicron-B.1.1.529 leads to widespread escape from 329 neutralizing antibody responses. bioRxiv Broadly neutralizing antibodies overcome SARS-CoV-2 Distinct BCR repertoires elicited by SARS-CoV-2 RBD and S 333 vaccinations in mice SARS-CoV-2 neutralizing antibody structures inform 335 therapeutic strategies week-old female mice were purchased from Beijing Vital River Animal Technology 360 Co., Ltd (licensed by Charles River). All of the mice used in this study are were 361 housed and bred in a temperature-, humidity-and light cycle-controlled SPF mouse 362 facilities in IMCAS (20±2℃; 50±10%; light, 7:00-19:00; dark, 19:00-7:00).