Abstract
Background
Increased community COVID-19 cases prompted the clinical evaluation of an mRNA-1273 booster dose (BD) in TeenCOVE adolescent participants (12-17 years) who received a 2-dose ...mRNA-1273 primary series. At ≥5 months after dose 2 (coinciding with the omicron wave peak in Jan 2022), TeenCOVE participants were offered an optional 50-µg mRNA-1273 BD. Here, we inferred BD effectiveness in adolescents by demonstrating non-inferiority (NI) of neutralizing antibody (nAb) responses post-BD vs young adults (18-25 years) post-dose 2 of 100-μg mRNA-1273 primary series in the pivotal phase 3 COVE study, where efficacy was established.
Methods
Up to 6 months post-BD, 1405 participants were monitored for COVID-19 and safety (solicited adverse reactions ≤7 days post-BD; unsolicited AEs ≤28 days post-BD; and medically attended, serious SAEs, of special interest AESI, or leading to discontinuation throughout study). At Day 29 post-BD, nAb geometric mean concentrations (GMCs) were measured against ancestral D614G SARS-CoV-2 spike protein. Binding antibodies (bAbs) against spike protein of ancestral strain or alpha, beta, delta, and gamma variants were measured.
Results
An mRNA-1273 BD was generally well-tolerated; reactogenicity profiles were consistent to the phase 3 COVE study in young adults. There were no severe COVID-19 cases, deaths, or investigator-reported vaccine-related SAEs or AESIs. In pre-booster SARS-CoV-2 negative participants, the ratio of adolescent (n=264) BD-Day 29 GMC (7102; 95% CI, 6553.2-7696.8) to young adult (n=294) Day 57 GMC (1400.4; 1272.7-1541.0) was 5.1 (4.5-5.7), meeting NI criterion for GMR (Fig 1; Table 1). The group difference in seroresponse rate (SRR) between adolescents and young adults was 0.7% (95% CI, -0.8 to 2.4), meeting NI criterion for SRR difference (Table 1). Robust bAb responses were observed, including against variants.
Conclusion
Effectiveness of an mRNA-1273 BD against COVID-19 in adolescents was inferred by successful immunobridging to young adults in the pivotal phase 3 trial. The benefits of variant-containing mRNA-1273 boosters demonstrated in adults is also anticipated to be conferred to adolescents. The overall benefit-risk profile of an mRNA-1273 BD is favorable in adolescents.
Disclosures
Amparo Figueroa, MD, MPH, Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Gary Berman, MD, Moderna, Inc.: Grant/Research Support Honghong Zhou, Ph.D., Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Weiping Deng, PhD, Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Monali Patel, MS, Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Bethany Girard, Ph.D., Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Anne Yeakey, MD, Moderna, Inc.: Advisor/Consultant Karen Slobod, MD, Moderna, Inc.: Advisor/Consultant Frances Priddy, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Jacqueline Miller, MD, Moderna, Inc.: salary|Moderna, Inc.: Stocks/Bonds Rituparna Das, M.D., Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds
Patients who died were older (mean age, 69 vs 65.1 years, P<0.023), and had higher rates of previous myocardial infarction (MI), (24.4% vs 8.4%, P<0.0001), congestive heart failure (85.9% vs 73.3%, ...P=0.012), peripheral vascular disease (16.7% vs 8.5%, P= 0.019), chronic lung disease (26.9% vs 17.1%, P=0.021), and chronic renal disease (35.9% vs 23.1, P=0.007).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The primary end point was reverse LV remodeling, which was defined as a composite of improvement in LVEF, LVEDD or severity of MR. Results: On Cox proportional hazard model non-AAs were twice as ...likely as AAs to have improvement in the primary endpoint at 12 months (HR 1.97, 95% CI: 1.21 to 3.84, p = 0.04) and 24 months (HR 1.72, 95% CI: 1.21 to 2.94, p = 0.04) after initiation of GDMT.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study investigated whether there is a difference in pulmonary function between healthy adult US-born Asian Indians and immigrant Asian Indians attributable to country of birth, environmental, ...and socioeconomic factors.
FEV1, FVC, and forced mid-expiratory flow between 25% and 75% of vital capacity (FEF25–75) were measured in India-born and US-born subjects residing in the Chicago metropolitan area. Hollingshead Index of Social Position was used to evaluate socioeconomic factors.
There were 262 India-born (61.8% male), and 200 US-born (50% male) subjects who were healthy lifelong nonsmokers; their age range was 16 to 36 years. US-born Asian Indian men and women were taller and had higher pulmonary function values for height and age compared with immigrant Asian Indian men and women. The differences were most pronounced in women: about 7% for FVC, 9% for FEV1, and 17% for FEF25–75. Immigrant and US-born subjects did not differ in socioeconomic position.
We conclude that US-born Asian Indian men and women have higher pulmonary function values for age and height compared with immigrant Asian Indian men and women. This probably reflects the effect of differing environmental conditions, which cause year-of-birth trends in lung volumes.
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