Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge.
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ABSTRACT:
SUBMITTER: Baden LR
PROVIDER: S-EPMC8609569 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge.
Baden Lindsey R LR El Sahly Hana M HM Essink Brandon B Follmann Dean D Neuzil Kathleen M KM August Allison A Clouting Heather H Fortier Gabrielle G Deng Weiping W Han Shu S Zhao Xiaoping X Leav Brett B Talarico Carla C Girard Bethany B Paila Yamuna D YD Tomassini Joanne E JE Schödel Florian F Pajon Rolando R Zhou Honghong H Das Rituparna R Miller Jacqueline J
The New England journal of medicine 20211103 26
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Project description:The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial. While mRNA-1273 demonstrated high efficacy in prevention of COVID-19, including severe disease, its effect on the viral dynamics of SARS-CoV-2 infections is not understood. Here, in exploratory analyses, we assessed the impact of mRNA-1273 vaccination in the ongoing COVE trial (number NCT04470427) on SARS-CoV-2 copy number and shedding, burden of disease and infection, and viral variants. Viral variants were sequenced in all COVID-19 and adjudicated COVID-19 cases (n = 832), from July 2020 in the blinded part A of the study to May 2021 of the open-label part B of the study, in which participants in the placebo arm started to receive the mRNA-1273 vaccine after US Food and Drug Administration emergency use authorization of mRNA-1273 in December 2020. mRNA-1273 vaccination significantly reduced SARS-CoV-2 viral copy number (95% confidence interval) by 100-fold on the day of diagnosis compared with placebo (4.1 (3.4-4.8) versus 6.2 (6.0-6.4) log10 copies per ml). Median times to undetectable viral copies were 4 days for mRNA-1273 and 7 days for placebo. Vaccination also substantially reduced the burden of disease and infection scores. Vaccine efficacies (95% confidence interval) against SARS-CoV-2 variants circulating in the United States during the trial assessed in this post hoc analysis were 82.4% (40.4-94.8%) for variants Epsilon and Gamma and 81.2% (36.1-94.5%) for Epsilon. The detection of other, non-SARS-CoV-2, respiratory viruses during the trial was similar between groups. While additional study is needed, these data show that in SARS-CoV-2-infected individuals, vaccination reduced both the viral copy number and duration of detectable viral RNA, which may be markers for the risk of virus transmission.
| S-EPMC9018421 | biostudies-literature
Project description:ImportanceNo studies to date have evaluated the effectiveness of 3 COVID-19 vaccines in the US military population, especially during the circulation of the SARS-CoV-2 Delta (B.1.617.2) variant.ObjectiveTo estimate the effectiveness of the mRNA-1273, BNT162b2, and JNJ-78436735 vaccines among US military personnel before and during the predominance of the Delta variant in the US.Design, setting, and participantsThis case-control study was conducted among all unvaccinated and fully vaccinated US military personnel who had a documented SARS-CoV-2 test performed in the US between January 1 and September 24, 2021. Individuals were identified using Department of Defense (DOD) electronic medical, laboratory, and surveillance databases. The pre-Delta period was defined as January 1 to May 31, 2021, and the Delta period as June 19 to September 24, 2021. Case individuals were defined by a positive polymerase chain reaction SARS-CoV-2 test result or a positive antigen test result with symptoms. Control individuals had at least 1 negative SARS-CoV-2 test result.ExposuresCOVID-19 vaccination with the mRNA-1273, BNT162b2, or JNJ-78436735 vaccine, assessed from DOD electronic vaccination records.Main outcomes and measuresCOVID-19 vaccine effectiveness overall, by vaccine type, and by outcome stratified by the pre-Delta and Delta periods in the US. Vaccine effectiveness was estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders.ResultsThe cohort included 441 379 individuals, with 290 256 in the pre-Delta period (236 555 [81%] male; median age, 25 years [range, 17-68 years]) and 151 123 in the Delta period (120 536 [80%] male; median age, 26 years [range, 17-70 years]). Adjusted vaccine effectiveness of all vaccines was significantly higher during the pre-Delta period (89.2%; 95% CI, 88.1%-90.1%) compared with the Delta period (70.2%; 95% CI, 69.3%-71.1%) for all outcomes, an overall decrease of 19%. mRNA-1273 vaccine effectiveness was highest in the pre-Delta (93.5%; 95% CI, 91.9%-94.7%) and Delta (79.4%; 95% CI, 78.3%-80.4%) periods for all outcomes, whereas the JNJ-78436735 vaccine had the lowest effectiveness during the pre-Delta (81.8%; 95% CI, 74.2%- 87.1%) and Delta (38.3%; 95% CI, 34.5%-41.9%) periods. Effectiveness for all vaccines during both periods was higher for symptomatic infection and hospitalization among individuals with SARS-CoV-2 infection.Conclusions and relevanceIn this case-control study, among US military personnel, COVID-19 vaccine effectiveness was significantly lower during the period when the Delta variant predominated compared with the period before Delta variant predominance; this was especially true for the JNJ-78436735 vaccine. These findings were confounded by time since vaccination; this and the change in effectiveness support the need for booster doses and continued evaluation of vaccine effectiveness as new variants of SARS-CoV-2 emerge.
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| S-EPMC10881222 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case-control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron or Delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variants determined by S gene target failure status (16% Delta and 84% Omicron). The two-dose VE against Omicron infection at 14-90 days was 44.0% (95% confidence interval, 35.1-51.6%) but declined quickly. The three-dose VE was 93.7% (92.2-94.9%) and 86.0% (78.1-91.1%) against Delta infection and 71.6% (69.7-73.4%) and 47.4% (40.5-53.5%) against Omicron infection at 14-60 days and >60 days, respectively. The three-dose VE was 29.4% (0.3-50.0%) against Omicron infection in immunocompromised individuals. The three-dose VE against hospitalization with Delta or Omicron was >99% across the entire study population. Our findings demonstrate high, durable three-dose VE against Delta infection but lower effectiveness against Omicron infection, particularly among immunocompromised people. However, three-dose VE of mRNA-1273 was high against hospitalization with Delta and Omicron variants.
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Project description:BackgroundMessenger RNA (mRNA)-1273 vaccine demonstrated 93.2% efficacy against coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial. The humoral immunogenicity results are now reported.MethodsParticipants received 2 mRNA-1273 (100 µg) or placebo injections, 28 days apart. Immune responses were evaluated in a prespecified, randomly selected per-protocol immunogenicity population (n = 272 placebo; n = 1185 mRNA-1273). Serum binding antibodies (bAbs) and neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike protein were assessed at days 1, 29, and 57 by baseline SARS-CoV-2-negative (n = 1197) and SARS-CoV-2-positive (n = 260) status, age, and sex.ResultsSARS-CoV-2-negative vaccinees had bAb geometric mean AU/mL levels of 35 753 at day 29 that increased to 316 448 at day 57 and nAb inhibitory dilution 50% titers of 55 at day 29 that rose to 1081 at day 57. In SARS-CoV-2-positive vacinees, the first mRNA-1273 injection elicited bAb and nAb levels that were 11-fold (410 049) and 27-fold (1479) higher than in SARS-CoV-2-negative vaccinees, respectively, and were comparable to levels after 2 injections in uninfected participants. Findings were generally consistent by age and sex.ConclusionsmRNA-1273 elicited robust serologic immune responses across age, sex, and SARS-CoV-2 status, consistent with its high COVID-19 efficacy. Higher immune responses in those previously infected support a booster-type effect. Clinical Trials Registration. NCT04470427.
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Project description:While mRNA vaccines are highly efficacious against short-term COVID-19, long-term immunogenicity is less clear. We compared humoral immunogenicity between BNT162b2 and mRNA-1273 vaccines 6 months after the first vaccine dose, examining the wild-type strain and multiple Delta-variant lineages. Using samples from a prospective observational cohort study of adult paramedics, we included COVID-19-negative participants who received two BNT162b2 or mRNA-1273 vaccines, and provided a blood sample 170 to 190 days post first vaccine dose. We compared wild-type spike IgG concentrations using the Mann-Whitney U test. We also compared secondary outcomes of: receptor binding domain (RBD) wild-type antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to spike proteins from the wild-type strain and five Delta-variant lineages. We included 571 adults: 475 BNT162b2 (83%) and 96 mRNA-1273 (17%) vaccinees, with a mean age of 39 (SD = 10) and 43 (SD = 10) years, respectively. Spike IgG antibody concentrations were significantly higher (P < 0.0001) for those who received mRNA-1273 (GM 601 BAU/mL [GSD 2.05]) versus BNT162b2 (GM 375 BAU/mL [GSD 2.33) vaccines. Results of RBD antibody comparisons (P < 0.0001), and inhibition of ACE-2 binding to the wild-type strain and all tested Delta lineages (all P < 0.0001), were consistent. Adults who received two doses of mRNA-1273 vaccines demonstrated improved wild-type and Delta variant-specific humoral immunity outcomes at 6 months compared with those who received two doses of the BNT162b2 vaccine. IMPORTANCE The BNT162b2 and mRNA-1273 mRNA SARS-CoV-2 vaccines have demonstrated high efficacy for preventing short-term COVID-19. However, comparative long-term effectiveness is unclear, especially pertaining to the Delta variant. We tested virus-specific antibody responses 6 months after the first vaccine dose and compared individuals who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines. We found that individuals who received the mRNA-1273 vaccine demonstrated superior serological markers at 6 months in comparison with those who received the BNT162b2 vaccine.
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