mRNA Vaccines Enhance Neutralizing Immunity against SARS-CoV-2 Variants in Convalescent and ChAdOx1-Primed Subjects

Fabricius, Dorit; Ludwig, Carolin; Scholz, Jochen; Rodé, I; Tsamadou, Chrysanthi; Jacobsen, Eva‐Maria; Winkelmann, Martina; Grempels, Aline; Lotfi, Ramin; Janda, Aleš; Körper, Sixten; Adler, Guido; Debatin, Klaus‐Michael; Schrezenmeier, Hubert; Jahrsdörfer, Bernd

doi:10.3390/vaccines9080918

Cited by 40 publications

(59 citation statements)

References 27 publications

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“…13 , 14 , 15 , 16 , 17 There is accruing evidence that the use of an mRNA boost after adenoviral-vector prime might enhance humoral and cellular responses against SARS-CoV-2, and that this response translates to efficacy against COVID-19. 8 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 The only other available data regarding heterologous schedules comes from preprints that suggest that adenoviral vaccines might be an effective boost for inactivated whole-virion prime. 30 , 31 …”

Section: Introductionmentioning

confidence: 99%

Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

et al. 2022

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Background Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). Methods Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. Findings Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. Interpretation Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. Funding UK Vaccine Task Force, Coalition for Epidemi...

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Section: Introductionmentioning

confidence: 99%

Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

et al. 2022

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“…As the vaccination race continues [ 25 ] worldwide, Romanian professionals in the sanitary and social fields will form an opinion on COVID-19 and its prophylaxis through vaccination and may support this campaign while decreasing the number of those who reject vaccination.…”

Section: Discussionmentioning

confidence: 99%

Early COVID-19 Vaccination of Romanian Medical and Social Personnel

Manolescu

Zaharia²,

Dumitrescu

et al. 2021

Vaccines

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Background: In December 2020, the first doses of COVID-19 vaccines arrived in Romania and were made available to medical and social staff. Vaccine hesitancy appeared as a barrier to effectively ending the pandemic. The opinions of medical and social staff influence the opinion of the general population. This study assesess the attitudes, knowledge, and opinion of medical and social personnel toward COVID-19 vaccines and vaccination and the influencing factors. Methods: 1025 persons participated in an online cross-sectional study from March until July 2021. Results: Out of 1021 eligible responders, 719 (70.42%) had been vaccinated: 227 with one dose (22.23%) and 492 with two doses (48.18%). There were 302 responders who were not vaccinated at all. Out of them, 188 refused vaccinations. The participants showed a good understanding and knowledge of SARScoV-2 transmission and treatment. Geographic area, medical profession, and medical experience influenced COVID-19 vaccination (p < 0.001). There were no associations between willingness to vaccinate and vaccine/virus knowledge. Most of the responders who were vaccinated or wanted to be vaccinated indicated an mRNA vaccine as their first choice. The variables that were significantly associated with reporting COVID-19 vaccine acceptance after logistic regression were: living in an urban area (Ora = 1.58, 95% CI: 0.98–2.56), being female (Ora = 1.59; 95% CI:1.03–2.44), and being a medical doctor (Ora = 3.40; 95% CI: 1.84–6.26). Conclusions: These findings show that vaccine hesitancy persists in medical and social personnel in Romania, and, hence, it may be reflected in the hesitancy of the general population toward vaccination.

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“…Nevertheless, little is still known about immune responses in elderly individuals who recovered from COVID-19 as compared to COVID-19-negative individuals or individuals with a longer interval to their previous infection. This comparison is particularly important in the context of currently emerging SARS-CoV-2 variants of concern (VOCs), particularly B.1.351 and P.1 (15)(16)(17). Primary aim of the present study was to assess the dynamics of humoral immune responses before and after first and second vaccination with BNT162b2 in individuals of different age and post-COVID-19 immune status.…”

Section: Introductionmentioning

confidence: 99%

BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents

et al. 2021

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Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1st and 3 weeks after 2nd vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2nd vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.

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mRNA Vaccines Enhance Neutralizing Immunity against SARS-CoV-2 Variants in Convalescent and ChAdOx1-Primed Subjects

Cited by 40 publications

References 27 publications

Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

Early COVID-19 Vaccination of Romanian Medical and Social Personnel

BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents

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