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Heterologous immunization with adenovirus vectored and inactivated vaccines effectively protects against SARS-CoV-2 variants in mice and macaques.

ABSTRACT: To cope with the decline in COVID-19 vaccine-induced immunity caused by emerging SARS-CoV-2 variants, a heterologous immunization regimen using chimpanzee adenovirus vectored vaccine expressing SARS-CoV-2 spike (ChAd-S) and an inactivated vaccine (IV) was tested in mice and non-human primates (NHPs). Heterologous regimen successfully enhanced or at least maintained antibody and T cell responses and effectively protected against SARS-CoV-2 variants in mice and NHPs. An additional heterologous booster in mice further improved and prolonged the spike-specific antibody response and conferred effective neutralizing activity against the Omicron variant. Interestingly, priming with ChAd-S and boosting with IV reduced the lung injury risk caused by T cell over activation in NHPs compared to homologous ChAd-S regimen, meanwhile maintained the flexibility of antibody regulation system to react to virus invasion by upregulating or preserving antibody levels. This study demonstrated the satisfactory compatibility of ChAd-S and IV in prime-boost vaccination in animal models.

SUBMITTER: He Q

PROVIDER: S-EPMC9428284 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Heterologous immunization with adenovirus vectored and inactivated vaccines effectively protects against SARS-CoV-2 variants in mice and macaques.

He Qian Q Mao Qunying Q Zhang Jialu J Gao Fan F Bai Yu Y Cui Bopei B Liu Jianyang J An Chaoqiang C Wang Qian Q Yan Xujia X Yang Jinghuan J Song Lifang L Song Ziyang Z Liu Dong D Yuan Yadi Y Sun Jing J Zhao Jincun J Bian Lianlian L Wu Xing X Huang Weijin W Li Changgui C Wang Junzhi J Liang Zhenglun Z Xu Miao M

Frontiers in immunology 20220817

To cope with the decline in COVID-19 vaccine-induced immunity caused by emerging SARS-CoV-2 variants, a heterologous immunization regimen using chimpanzee adenovirus vectored vaccine expressing SARS-CoV-2 spike (ChAd-S) and an inactivated vaccine (IV) was tested in mice and non-human primates (NHPs). Heterologous regimen successfully enhanced or at least maintained antibody and T cell responses and effectively protected against SARS-CoV-2 variants in mice and NHPs. An additional heterologous boo ...[more]

PMID: 36059554

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Project description:BackgroundImpaired immune responses to COVID-19 vaccines have been observed in autoimmune rheumatic disease patients. Determining the most effective and safe vaccine regimen is critically needed in such a population. We aim to compare the immunogenicity and safety of three COVID-19 vaccine regimens in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsSLE and RA patients aged 18-65 years who received inactivated (CoronaVac or COVILO), adenovirus-vectored (AZD1222), or heterogeneous (AZD1222/BNT162b2) vaccines were enrolled. Humoral and cellular immune responses were assessed at day 28 after the second vaccination. This was performed using the serum binding antibody level against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD Ig) and IFNy-ELISpot assay (ELISpot), respectively. Reactogenicity was reviewed on day 7 following each vaccination. Disease activity was assessed before and on day 28 after the second vaccination.ResultsThe cohort consisted of 94 patients (64 SLE and 30 RA). Inactivated, AZD1222, and AZD1222/BNT162b2 vaccines were administered to 23, 43, and 28 patients, respectively. Anti-RBD titers were lowest in the inactivated vaccine group (2.84 AU/mL; 95% CI 0.96-8.44), followed by AZD1222 (233.7 AU/mL; 95% CI 99.0-505.5), and AZD1222/BNT162b2 (688.6 AU/mL; 95% CI 271-1745), p < 0.0001. After adjusting for relevant factors, the inactivated vaccine was associated with the lowest humoral response, while adenovirus-vectored/mRNA vaccine was the highest. The proportion of positive ELISpot test was also lowest in the inactivated vaccine group (27%), followed by the adenovirus-vectored vaccine (67%), and the adenovirus-vectored/mRNA vaccine (73%) (p = 0.03). All types of vaccine were well-tolerated. There was no flare of autoimmune disease post-vaccination.ConclusionAdenovirus-vectored and adenovirus-vectored/mRNA vaccines elicited a stronger humoral and cellular immune response than inactivated vaccines, suggesting that they may be more suitable in SLE and RA patients receiving immunosuppressive therapy.

Project description:Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-naïve individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV increased IgG responses against A/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A/H1N1-HA after each vaccine dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-γ-producing CD4+ T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral responses are significantly increased in scope and magnitude, advocating WPV vaccination regimens for priming immunologically-naïve individuals and also in the event of a pandemic outbreak.

Dataset Information

Heterologous immunization with adenovirus vectored and inactivated vaccines effectively protects against SARS-CoV-2 variants in mice and macaques.

Publications

Heterologous immunization with adenovirus vectored and inactivated vaccines effectively protects against SARS-CoV-2 variants in mice and macaques.

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