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Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

ABSTRACT: Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Our results showed that the humoral and cellular immune responses induced by different vaccines when administered individually differ significantly. In particular, inactivated vaccines showed relatively lower level of neutralizing antibody and T cell responses, but a higher IgG2a/IgG1 ratio compared with other vaccines. Boosting with either recombinant subunit, adenovirus vectored or mRNA vaccine after two-doses of inactivated vaccine further improved both neutralizing antibody and Spike-specific Th1-type T cell responses compared to boosting with a third dose of inactivated vaccine. Our results provide new ideas for prophylactic inoculation strategy of SARS-CoV-2 vaccines.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8381941 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

Zhang Jialu J He Qian Q An Chaoqiang C Mao Qunying Q Gao Fan F Bian Lianlian L Wu Xing X Wang Qian Q Liu Pei P Song Lifang L Huo Yaqian Y Liu Siyuan S Yan Xujia X Yang Jinghuan J Cui Bopei B Li Changgui C Wang Junzhi J Liang Zhenglun Z Xu Miao M

Emerging microbes & infections 20211201 1

Since the outbreak of COVID-19, a variety of vaccine platforms have been developed. Amongst these, inactivated vaccines have been authorized for emergency use or conditional marketing in many countries. To further enhance the protective immune responses in populations that have completed vaccination regimen, we investigated the immunogenic characteristics of different vaccine platforms and tried homologous or heterologous boost strategy post two doses of inactivated vaccines in a mouse model. Ou ...[more]

PMID: 34278956

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Project description:Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

Project description:ImportanceEvidence for the timing of booster vaccination after completion of BNT162b2 and CoronaVac primary vaccination is crucial to guide policy recommendations.ObjectiveTo compare the odds of symptomatic SARS-CoV-2 infection and COVID-19-related outcomes after heterologous and homologous boosting of CoronaVac at 3-month intervals and homologous boosting of BNT162b2 at 6-month intervals, with BNT162b2 primary series (2 doses) as the reference group.Design, setting, and participantsThis population-based retrospective cohort study used national data for Malaysia. Participants included all individuals aged 18 years and older who received a complete primary series of CoronaVac or BNT162b2 vaccine and were eligible for a booster dose between November 21, 2021, and December 28, 2021. Data were analyzed from November 21, 2021, to January 7, 2022.ExposuresReceipt of a booster vs no booster and categorized into primary series BNT162b2 (2 doses of BNT162b2), primary series CoronaVac (2 doses of CoronaVac), 3 doses of BNT162b2, primary series CoronaVac plus a BNT162b2 booster, and 3 doses of CoronaVac.Main outcomes and measuresThe primary outcome was symptomatic SARS-CoV-2 infection. The secondary outcomes were COVID-19-related intensive care unit admission and death. All outcomes were observed from the day an individual was considered fully boosted (≥14 days after booster dose).ResultsOur cohort included 13 840 240 individuals (mean [SD] age, 39.9 [15.5] years; 7 040 298 [50.9%] men; 4 451 180 individuals [32.2%] with ≥1 comorbidities), of whom 5 081 641 individuals (36.7%) had received a booster dose. Using the primary series BNT162b2 recipients as reference, the adjusted odds against symptomatic SAR-CoV-2 infection were lower for individuals who received the primary series CoronaVac plus a BNT162b2 (adjusted odds ratio [aOR], 0.06 [95% CI, 0.05-0.06]), 3 doses of CoronaVac (aOR, 0.08 [95% CI, 0.06-0.10]), or 3 doses of BNT162b2 (aOR, 0.01 [95% CI, 0.00-0.01]). Receipt of heterologous booster (primary series of CoronaVac plus a BNT162b2 booster) was associated with lower odds of SARS-CoV-2 infection (aOR, 0.17 [95% CI, 0.17-0.18]) compared with homologous booster (3 doses of CoronaVac) for individuals aged 60 years and older (aOR, 0.19 [95% CI, 0.19-0.20]).Conclusions and relevanceIn this cohort study, for individuals who received the CoronaVac primary series and a booster dose of BNT162b2 or CoronaVac at 3 months, the observed odds of symptomatic SARS-CoV-2 infection were similar to individuals who received the BNT162b2 primary series plus a third dose of BNT162b2 at 6 months. Heterologous booster is recommended for individuals aged 60 years or older who received the CoronaVac primary series, given the lower observed odds against symptomatic SARS-CoV-2 infection among those who received a BNT1612b2 booster.

Dataset Information

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

Publications

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine.

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