Efficacy, immunogenicity, and safety of a next-generation #mRNA-1283 #COVID19 #vaccine compared with mRNA-1273 vaccine (NextCOVE)...

Summary

Background

mRNA-1283 is an investigational, next-generation COVID-19 vaccine that encodes only the immunodominant regions of the SARS-CoV-2 spike protein—the receptor-binding domain (RBD) and the N-terminal domain rather than the full-length spike used in currently authorised mRNA vaccines. We evaluated the relative vaccine efficacy (rVE), immunogenicity, and safety of mRNA-1283 compared to the first-generation vaccine (mRNA-1273).

Methods

This randomised, observer-masked, active-controlled, phase 3 trial (NextCOVE) was conducted in individuals (aged ≥12 years) with no evidence of SARS-CoV-2 infection within 90 days of screening in the USA, the UK, and Canada. Participants were randomly assigned in a 1:1 ratio to receive one 10 μg dose of the bivalent formulation of mRNA-1283 (original plus omicron BA.4/BA.5) or 50 μg of the bivalent mRNA-1273, encoding the same variants. Randomisation was stratified by age (12–17 years, 18–64 years, and ≥65 years). Primary objectives comparing mRNA-1283 with mRNA-1273 were non-inferior rVE to prevent a first event of COVID-19 from 14 days after study injection to the end of follow-up (assessed in the per-protocol set for efficacy, with non-inferiority declared when the lower bound of the α-adjusted two-sided CI for rVE was greater than –10%), non-inferior immunogenicity at day 29 (assessed in the per-protocol immunogenicity subset, with non-inferiority declared when the lower bounds of the CIs for the geometric mean concentration ratios [GMRs] of neutralising antibodies against SARS-CoV-2 D614G and omicron BA.4/BA.5 were >0·667 and the lower bounds of the 95% CI seroresponse rate differences for the two variants were greater than –10%), and safety (assessed in the safety set, which included all participants who received a vaccination). The trial is registered at ClinicalTrials.gov (NCT05815498) and is complete.

Findings

Between March 28 and Aug 23, 2023, we screened 13 054 individuals for eligibility and randomly allocated 11 454 participants (5728 to mRNA-1283 and 5726 to mRNA-1273). 1177 confirmed COVID-19 events occurred up to Jan 31, 2024 (560 [9·9%] of 5679 in mRNA1283.222 and 617 [10·8%] of 5687 in mRNA-1273.222). The median age of participants at enrolment was 56 years (IQR 38–66). Of the 11 417 participants who received a vaccine, 6200 (54·3%) were female and 5217 (45·7%) were male; 9381 (82·2%) were White; and 1510 (13·2%) were Hispanic or Latino. Of the total cohort, 992 (8·7%) participants were aged 12–17 years, 7151 (62·6%) were aged 18–64 years, and 3274 (28·7%) were 65 years and older; in addition, 6857 participants (60·1%) were 50 years and older. The rVE point estimate was 9·3% (99·4% CI –6·6 to 22·8; p=0·0005). The GMR was 1·3 (95% CI 1·2 to 1·5) for BA.4/BA.5 and 1·2 (1·1 to 1·4) for D614G. The day-29 seroresponse rate difference was 14·4% (95% CI 9·3 to 19·4) for BA.4/BA.5 and 10·7% (6·0 to 15·4) for D614G. Local and systemic adverse reactions were similar between mRNA-1283 and mRNA-1273; mRNA-1283 was associated with fewer injection-site pain reactions than mRNA-1273 (3905 [68·5%] of 5701 vs 4419 [77·5%] of 5705, respectively). The frequency of unsolicited adverse events, serious adverse events, and medically attended adverse events were similar between groups during the first 28 days after injection. One event of sudden death occurred in a participant with underlying cardiovascular disease in the mRNA-1273 group; it was reported as related to vaccination due to its temporal association.

Interpretation

mRNA-1283 was well-tolerated. The rVE and immunogenicity non-inferiority criteria were met, with higher antibody responses for mRNA-1283 versus mRNA-1273. The potential clinical benefit of mRNA-1283 versus mRNA-1273 needs to be confirmed in post-marketing evaluation.

Funding

Moderna.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00236-1/fulltext?rss=yes

____

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...

ETIDIOH - NEW

Search This Blog