Recombinant protein subunit vaccine booster following two-dose inactivated vaccines dramatically enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and Variants of Concern

Ai, Jingwen; Zhang, Haocheng; Zhang, Qiran; Zhang, Yi; Lin, Ke; Fu, Zhangfan; Song, Jun Young; Zhao, Ying; Fan, Mingxiang; Wang, Hongyu; Qiu, Chao; Zhou, Yang; Zhang, Wenhong

doi:10.1038/s41422-021-00590-x

Cited by 82 publications

(98 citation statements)

References 10 publications

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“…Then we turned our attention to the efficacy of booster shots now routinely administered in many countries and reported to induce higher immune response [ 9 ]. This time, to measure and clarify the efficacy of vaccine boosters against the Omicron variant, we collected samples from healthy adults who had a third boosting vaccination shot with either an inactivated whole-virion vaccine (BBIBP-CorV, homologous booster group) or a protein subunit vaccine (ZF2001, heterologous booster group) administered at an interval of 4–8 months following previous priming vaccination by two doses of BBIBP-CorV vaccine (Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Wang

Zhao

Song

et al. 2022

Emerging Microbes & Infections

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119

111

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The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera from convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists seven of eight authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

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Section: Resultsmentioning

confidence: 99%

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Wang

Zhao

Song

et al. 2022

Emerging Microbes & Infections

Self Cite

119

111

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“…The blood samples from this heterologous booster vaccination group also showed a rapid rise of nAbs titers, reaching levels that were about three times more than those in the homologous vaccination group. Of note, while this manuscript was in preparation, several studies were published, which examined the reactogenicity and immunogenicity of inactivated vaccine-primed individuals (CoronaVac or BBIBP-CorV) after receiving a third dose of a homologous vaccine or a heterologous vaccine (ZF2001, an RBD dimer subunit recombinant vaccine) [17][18][19]. In these studies, a third dose elicited enhanced humoral immunity against multiple SARS-CoV-2 variants, including the highly infectious Delta variant [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…Of note, while this manuscript was in preparation, several studies were published, which examined the reactogenicity and immunogenicity of inactivated vaccine-primed individuals (CoronaVac or BBIBP-CorV) after receiving a third dose of a homologous vaccine or a heterologous vaccine (ZF2001, an RBD dimer subunit recombinant vaccine) [17][18][19]. In these studies, a third dose elicited enhanced humoral immunity against multiple SARS-CoV-2 variants, including the highly infectious Delta variant [17][18][19]. Though we used a different priming (BBIBP-CorV vs. CoronaVac) or booster (NVSI-06-08 vs. ZF2001) vaccine, our study support that both homologous and heterologous vaccinations could boost the immunity of individuals previously vaccinated by inactivated virus vaccines.…”

Section: Discussionmentioning

confidence: 99%

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults

Zhang¹,

Yang²,

Qiao

et al. 2022

Front. Med.

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Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11684-021-0914-x and is accessible for authorized users.

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“…Then we turned our attention to the efficacy of booster shots now routinely administered in many countries and reported to induce higher immune response 9 . This time, to measure and clarify the efficacy of vaccine boosters against the Omicron variant, we collected samples from healthy adults who had a third boosting vaccination shot with either an inactivated whole-virion vaccine (BBIBP-CorV, homologous booster group) or a protein subunit vaccine (ZF2001, hoterogous booster group) administered at an interval of 4–8 months following previous priming vaccination by two doses of BBIBP-CorV vaccine (Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

Wang

Zhao

Song

et al. 2021

Preprint

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The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

show abstract

Recombinant protein subunit vaccine booster following two-dose inactivated vaccines dramatically enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and Variants of Concern

Cited by 82 publications

References 10 publications

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults

Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

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