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Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

ABSTRACT: Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous inactivated COVID-19 vaccine (CoronaVac) and adenoviral-vectored vaccine (AZD1222) were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 79) and AZD1222 (N = 78) regimen. All sera samples were tested for anti-receptor-binding-domain IgG (anti-RBD IgG) using a chemiluminescent microparticle immunoassay (CMIA). The neutralizing activity in a subset of serum samples was tested against the original Wuhan strain and variants of concern, B.1.1.7, B.1.617.2 and B.1.351, using an enzyme-linked immunosorbent assay (ELISA)-based surrogate virus neutralization test (sVNT). The heterologous CoronaVac/AZD1222 vaccine induced higher levels of anti-RBD IgG than that of two-dose homologous CoronaVac or AZD1222 vaccines (p < 0.001). Sera samples of the CoronaVac/AZD1222 vaccine recipients elicited higher neutralizing antibody activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. The heterologous CoronaVac followed by AZD1222 is an alternative regimen to combat with the SARS-CoV-2 variants in case of vaccine shortage with improved immunogenicity compared to the homologous CoronaVac regimen.

SUBMITTER: Wanlapakorn N

PROVIDER: S-EPMC9013645 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

Wanlapakorn Nasamon N Suntronwong Nungruthai N Phowatthanasathian Harit H Yorsaeng Ritthideach R Thongmee Thanunrat T Vichaiwattana Preeyaporn P Auphimai Chompoonut C Wongsrisang Lakkhana L Klinfueng Sirapa S Sudhinaraset Natthinee N Poovorawan Yong Y

Vaccine 20220418 23

Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous inactivated COVID-19 vaccine (CoronaVac) and adenoviral-vectored vaccine (AZD1222) were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 79) and AZD1222 (N = 78) regimen. All sera samples were tested for anti-receptor-bind ...[more]

PMID: 35465981

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Project description:BackgroundHeterologous prime-boost with ChAdOx1 nCoV-19 vector vaccine (ChAd) and a messenger RNA vaccine (BNT or mRNA-1273) has been widely facilitating mass coronavirus disease 2019 (COVID-19) immunisation. This review aimed to synthesize immunogenicity and reactogenicity of heterologous immunisations with ChAd and BNT (mRNA-1273) vaccine compared with homologous ChAd or BNT (mRNA-1273) immunisation.MethodsPubMed, Web of Science, and Embase databases were searched from inception to March 7, 2022. Immunogenicity involving serum antibodies against different SAS-CoV-2 fragments, neutralizing antibody, or spike-specific T cells response were compared. Any, local and systemic reactions were pooled by meta-analysis for comparison.ResultsOf 14,571 records identified, 13 studies (3024 participants) were included for analysis. Compared with homologous BNT/BNT vaccination, heterologous ChAd/BNT schedule probably induced noninferior anti-spike protein while higher neutralizing antibody and better T cells response. Heterologous ChAd/BNT (mRNA-1273) immunisation induced superior anti-spike protein and higher neutralizing antibody and better T cells response compared with homologous ChAd/ChAd vaccination. Heterologous ChAd/BNT (mRNA-1273) had similar risk of any reaction (RR = 1.30, 95% CI: 0.86-1.96) while higher risk of local reactions (RR = 1.65, 95% CI: 1.27-2.15) and systemic reactions (RR = 1.49, 95% CI: 1.17-1.90) compared with homologous ChAd/ChAd vaccination. There was a higher risk of local reactions (RR = 1.16, 95% CI: 1.03-1.31) in heterologous ChAd/BNT (mRNA-1273) vaccination compare with homologous BNT/BNT but a similar risk of any reaction (RR = 1.03, 95% CI: 0.79-1.34) and systemic reactions (RR = 0.89, 95% CI: 0.60-1.30).ConclusionsHeterologous ChAd/BNT schedule induced at least comparable immunogenicity compared with homologous BNT/BNT and better immunogenicity compared with homologous ChAd/ChAd vaccination. The synthetical evidence supported the general application of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.

Project description:BackgroundUse of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer-BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines.MethodsCom-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139.FindingsBetween Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation.InterpretationDespite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.FundingUK Vaccine Task Force and National Institute for Health Research.

Project description:Adenoviral vectors are a safe and potently immunogenic vaccine delivery platform. Non-replicating Ad vectors possess several attributes which make them attractive vaccines for infectious disease, including their capacity for high titer growth, ease of manipulation, safety, and immunogenicity in clinical studies, as well as their compatibility with clinical manufacturing and thermo-stabilization procedures. In general, Ad vectors are immunogenic vaccines, which elicit robust transgene antigen-specific cellular (namely CD8+ T cells) and/or humoral immune responses. A large number of adenoviruses isolated from humans and non-human primates, which have low seroprevalence in humans, have been vectorized and tested as vaccines in animal models and humans. However, a distinct hierarchy of immunological potency has been identified between diverse Ad vectors, which unfortunately limits the potential use of many vectors which have otherwise desirable manufacturing characteristics. The precise mechanistic factors which underlie the profound disparities in immunogenicity are not clearly defined and are the subject of ongoing, detailed investigation. It has been suggested that a combination of factors contribute to the potent immunogenicity of particular Ad vectors, including the magnitude and duration of vaccine antigen expression following immunization. Furthermore, the excessive induction of Type I interferons by some Ad vectors has been suggested to impair transgene expression levels, dampening subsequent immune responses. Therefore, the induction of balanced, but not excessive stimulation of innate signaling is optimal. Entry factor binding or receptor usage of distinct Ad vectors can also affect their in vivo tropism following administration by different routes. The abundance and accessibility of innate immune cells and/or antigen-presenting cells at the site of injection contributes to early innate immune responses to Ad vaccination, affecting the outcome of the adaptive immune response. Although a significant amount of information exists regarding the tropism determinants of the common human adenovirus type-5 vector, very little is known about the receptor usage and tropism of rare species or non-human Ad vectors. Increased understanding of how different facets of the host response to Ad vectors contribute to their immunological potency will be essential for the development of optimized and customized Ad vaccine platforms for specific diseases.

Project description:IntroductionCellular and humoral immune responses are both involved in protection against Plasmodium infections. The only malaria vaccine available, RTS,S, primarily induces short-lived antibodies and targets only a pre-erythrocytic stage antigen. Inclusion of erythrocytic stage targets and enhancing cellular immunogenicity are likely necessary for developing an effective second-generation malaria vaccine. Adenovirus vectors have been used to improve the immunogenicity of protein-based vaccines. However, the clinical assessment of adenoviral-vectored malaria vaccines candidates has shown the induction of robust Plasmodium-specific CD8+ but not CD4+ T cells. Signal peptides (SP) have been used to enhance the immunogenicity of DNA vaccines, but have not been tested in viral vector vaccine platforms.ObjectivesThe objective of this study was to determine if the addition of the SP derived from the murine IgGκ light chain within a recombinant adenovirus vector encoding a multistage P. vivax vaccine candidate could improve the CD4+ T cell response.MethodsIn this proof-of-concept study, we immunized CB6F1/J mice with either the recombinant simian adenovirus 36 vector containing the SP (SP-SAd36) upstream from a transgene encoding a chimeric P. vivax multistage protein or the same SAd36 vector without the SP. Mice were subsequently boosted twice with the corresponding recombinant proteins emulsified in Montanide ISA 51 VG. Immunogenicity was assessed by measurement of antibody quantity and quality, and cytokine production by T cells after the final immunization.ResultsThe SP-SAd36 immunization regimen induced significantly higher antibody avidity against the chimeric P. vivax proteins tested and higher frequencies of IFN-γ and IL-2 CD4+ and CD8+ secreting T cells, when compared to the unmodified SAd36 vector.ConclusionsThe addition of the murine IgGκ signal peptide significantly enhances the immunogenicity of a SAd36 vectored P. vivax multi-stage vaccine candidate in mice. The potential of this approach to improve upon existing viral vector vaccine platforms warrants further investigation.

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.

Dataset Information

Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

Publications

Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

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