Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination.
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ABSTRACT:
SUBMITTER: Normark J
PROVIDER: S-EPMC8314734 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination.
Normark Johan J Vikström Linnea L Gwon Yong-Dae YD Persson Ida-Lisa IL Edin Alicia A Björsell Tove T Dernstedt Andy A Christ Wanda W Tevell Staffan S Evander Magnus M Klingström Jonas J Ahlm Clas C Forsell Mattias M
The New England journal of medicine 20210714 11
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Project description:Background/purposeEfficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited.MethodsWe recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose.ResultsWe enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks.ConclusionHeterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368).
| S-EPMC8926322 | biostudies-literature
Project description:Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
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Project description:The appropriate interval between heterologous prime adenoviral vectored vaccination and boost mRNA vaccination remains unclear. We recruited 100 adult participants to receive a prime adenoviral vectored vaccine (ChAdOx1, AstraZeneca) and a boost mRNA vaccine (mRNA-1273, Moderna) 12 weeks apart and checked their serum SARS-CoV-2 anti-spike IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on the 28th day after the boost dose. Results were compared with our previous study cohorts who received the same prime-boost vaccinations at 4- and 8-week intervals. Compared to other heterologous vaccination groups, the 12-week interval group had higher neutralizing antibody titers against SARS-CoV-2 variants than the 4-week interval group and was similar to the 8-week interval group at day 28. Adverse reactions after the boost dose were mild and transient. Our results support deploying viral vectored and mRNA vaccines in a flexible schedule with intervals from 8 to 12 weeks.
| S-EPMC9385402 | biostudies-literature
Project description:(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0-491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0-159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.
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| S-EPMC8321428 | biostudies-literature
Project description:Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.
| S-EPMC9366133 | biostudies-literature
Project description:Heterologous prime-boost immunization strategies have the potential to augment COVID-19 vaccine efficacy. We longitudinally profiled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-specific serological and memory B cell (MBC) responses in individuals who received either homologous (ChAdOx1:ChAdOx1) or heterologous (ChAdOx1:mRNA-1273) prime-boost vaccination. Heterologous messenger RNA (mRNA) booster immunization induced higher serum neutralizing antibody and MBC responses against SARS-CoV-2 variants of concern (VOCs) compared with that of homologous ChAdOx1 boosting. Specificity mapping of circulating B cells revealed that mRNA-1273 boost immunofocused ChAdOx1-primed responses onto epitopes expressed on prefusion-stabilized S. Monoclonal antibodies isolated from mRNA-1273-boosted participants displayed overall higher binding affinities and increased breadth of reactivity against VOCs relative to those isolated from ChAdOx1-boosted individuals. Overall, the results provide molecular insight into the enhanced quality of the B cell response induced after heterologous mRNA booster vaccination.
| S-EPMC8939765 | biostudies-literature
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| S-EPMC9483497 | biostudies-literature
Project description:BackgroundThe effectiveness of heterologous prime-boost Coronavirus disease 2019 (Covid-19) vaccination is currently unknown.MethodsFrom individuals vaccinated with two doses against Covid-19 in Sweden until July 5, 2021 (N=3,445,061), we formed a study cohort including 94,569 individuals that had received heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, 16,402 individuals that received heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination, and 430,100 individuals that received homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 prime-boost vaccination. In addition, 180,716 individuals were selected who were unvaccinated at the date of vaccination in the corresponding case. Unvaccinated individuals were censored at first dose of any vaccine. Baseline was the date of the second dose of any vaccine, with the same date in the corresponding unvaccinated individual. The outcome included incident symptomatic Covid-19 infection occurring >14 days after baseline.FindingsDuring a mean follow-up time of 76 (range 1-183) days, symptomatic Covid-19 infection was confirmed in 187 individuals with heterologous vaccine schedules (incidence rate: 2.0/100,000 person-days) and in 306 individuals from the unvaccinated control group (incidence rate: 7.1/100,000 person-days). The adjusted vaccine effectiveness was 67% (95% CI, 59-73, P<0.001) for heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination, and 79% (95% CI, 62-88, P<0.001) for heterologous ChAdOx1 nCoV-19 / mRNA-1273 prime-boost vaccination. When combined and analysed together, the two heterologous vaccine schedules had an effectiveness of 68% (95% CI, 61-74, P<0.001) which was significantly greater (Pinteraction<0.001) than the 50% effectiveness for homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 (95% CI, 41-58, P<0.001).InterpretationThe findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period. These findings could have important implications for vaccination strategies and logistics, and consequently in the battle against the Covid-19 pandemic.
| S-EPMC8520818 | biostudies-literature
Project description:BackgroundHemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain.MethodsTo compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28).ResultsBoth mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination.ConclusionOur prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.
| S-EPMC10383458 | biostudies-literature