mRNA-1273.211 / Moderna - LARVOL DELTA

Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters. (PubMed, Front Immunol) - "Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster. Overall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination. (PubMed, J Med Virol) - "The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines."

Biomarker • Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Thrombocytopenia • MPO

A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 (COVID-19) Variants (clinicaltrials.gov) - P2/3 | N=5404 | Completed | Sponsor: ModernaTX, Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2 | N=867 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Jun 2023 | Trial primary completion date: Jun 2024 ➔ Jun 2023

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 (COVID-19) Variants (clinicaltrials.gov) - P2/3 | N=5404 | Active, not recruiting | Sponsor: ModernaTX, Inc. | Trial completion date: Apr 2023 ➔ Nov 2023 | Trial primary completion date: Apr 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2 | N=867 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2 | N=1130 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2023 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2 | N=1130 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Do We Really Need Omicron Spike-Based Updated COVID-19 Vaccines? Evidence and Pipeline. (PubMed, Viruses) - "An accelerated rate of immune escape to vaccine-elicited immunity has been associated with Spike protein antigenic shifts, as seen in the Omicron variant of concern and its sublineages, demanding the development of Omicron Spike-based vaccines. Herein, we review the evidence in animal models and topline results from ongoing clinical trials with such updated vaccines, discussing the pros and cons for their deployment."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial. (PubMed, Nat Med) - P2/3, P2a, P3 | "Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series ( NCT04927065 ). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants."

Journal • P2/3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 (COVID-19) Variants (clinicaltrials.gov) - P2/3 | N=4658 | Active, not recruiting | Sponsor: ModernaTX, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antibody responses to SARS-CoV-2 elicited by the multivalent, variant-matched booster mRNA-1273.211 vaccine among adults (ECCMID 2022) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 Variants (clinicaltrials.gov) - P2/3 | N=4720 | Recruiting | Sponsor: ModernaTX, Inc. | N=3620 ➔ 4720 | Trial completion date: Nov 2022 ➔ Mar 2023 | Trial primary completion date: Jun 2022 ➔ Mar 2023

Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. (PubMed, Vaccine) - "A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants (clinicaltrials.gov) - P2/3; N=3620; Recruiting; Sponsor: ModernaTX, Inc.; Active, not recruiting ➔ Recruiting; N=1768 ➔ 3620

Clinical • Enrollment change • Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2; N=950; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial completion date: May 2025 ➔ Dec 2022; Trial primary completion date: May 2023 ➔ Dec 2022

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. (PubMed, Nat Med) - P2a | "Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants (clinicaltrials.gov) - P2/3; N=1768; Active, not recruiting; Sponsor: ModernaTX, Inc.; N=896 ➔ 1768

Clinical • Enrollment change • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Delayed Heterologous SARS-CoV-2 Vaccine Dosing (Boost) After Receipt of EUA Vaccines (clinicaltrials.gov) - P1/2; N=800; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); N=550 ➔ 800

Enrollment change • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants (clinicaltrials.gov) - P2/3; N=896; Active, not recruiting; Sponsor: ModernaTX, Inc.; N=300 ➔ 896

Clinical • Enrollment change • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Moderna, Pfizer COVID-19 Vaccines Do Not Affect Male Fertility (HCPLive) - P=NA, N=45; "A research team from the University of Miami Miller School of Medicine assessed 45 healthy men (median age, 28 years) who received either the BNT162b2 mRNA vaccine (Pfizer-BioNTech) or the mRNA-1273 mRNA vaccine (Moderna)....'Vaccine hesitancy is a barrier to ending the COVID-19 pandemic, and we believe some of that hesitancy is due to public opinion about whether the vaccine might negatively affect fertility,' senior study author Ranjith Ramasamy...stated in a press release....In their study conclusion, the author's wrote, 'Because the vaccines contain mRNA and not the live virus, it is unlikely that the vaccine would affect sperm parameters.'"

Clinical data • Media quote

A Study to Evaluate the Immunogenicity and Safety of mRNA-1273.211 Vaccine for COVID-19 Variants (clinicaltrials.gov) - P2/3; N=300; Active, not recruiting; Sponsor: ModernaTX, Inc.

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Moderna Announces it has Shipped Variant-Specific Vaccine Candidate, mRNA-1273.351, to NIH for Clinical Study (Businesswire) - "Moderna, Inc....announces that it has completed manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351...and has shipped doses to the National Institutes of Health (NIH) for a Phase 1 clinical trial...First, the Company is evaluating booster doses of vaccine to increase neutralizing immunity against the variants of concern....Moderna plans to evaluate three approaches to boosting, including: A variant-specific booster candidate, mRNA-1273.351...at the 50 µg dose level and lower; A multivalent booster candidate, mRNA-1273.211...and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower; A third dose of mRNA-1273...as a booster at the 50 µg dose level....Second, the Company plans to evaluate mRNA-1273.351 and mRNA-1273.211 as a primary vaccination series for those who are seronegative. These candidates will be evaluated in a two-dose series at the 100 µg dose level and lower."

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease

Moderna Announces First Participants Dosed in Study Evaluating COVID-19 Booster Vaccine Candidates (Businesswire) - "...the first participants have been dosed with the Company’s modified COVID-19 vaccines...An amendment to the Phase 2 study will enroll 60 participants previously vaccinated with mRNA-1273 to receive a single booster dose of either: 20 µg of a variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in the Republic of South Africa (N=20); 50 µg of mRNA-1273.351 (N=20); 50 µg of a multivalent booster candidate, mRNA-1273.211...In parallel, NIAID, part of the National Institutes of Health (NIH), will conduct a Phase 1 clinical trial to assess the monovalent and multivalent modified mRNA-1273 vaccines..."

New P1 trial • Trial status • Infectious Disease • Novel Coronavirus Disease