Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge.
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ABSTRACT:
SUBMITTER: Baden LR
PROVIDER: S-EPMC8609569 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC9021911 | biostudies-literature
Project description: Not available
| S-EPMC8552536 | biostudies-literature
Project description: Not available
| 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.
| S-EPMC9117141 | biostudies-literature
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.
| S-EPMC9213865 | biostudies-literature
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.
| S-EPMC9045183 | biostudies-literature
Project description: Not available
| S-EPMC8809504 | biostudies-literature
Project description:A March-June 2021 representative serosurvey among Sitakunda subdistrict (Chattogram, Bangladesh) residents found an adjusted prevalence of severe acute respiratory syndrome coronavirus 2 antibodies of 64.1% (95% credible interval 60.0%-68.1%). Before the Delta variant surge, most residents had been infected, although cumulative confirmed coronavirus disease incidence was low.
| S-EPMC8798688 | biostudies-literature
Project description:Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6-8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2.
| S-EPMC9117133 | biostudies-literature
Project description:We conducted a retrospective review of medical records of patients with croup seen during the coronavirus disease 2019 pandemic. Approximately 50% underwent testing for severe acute respiratory syndrome coronavirus 2. During the Delta wave, 2.8% of those tested were positive for severe acute respiratory syndrome coronavirus 2; this increased to 48.2% during the Omicron wave, demonstrating a strong correlation between the Omicron variant and croup.
| S-EPMC9085454 | biostudies-literature