Comirnaty Bivalent Original/Omicron BA.1 (BNT162b2 Bivalent) / BioNTech, Pfizer - LARVOL DELTA

A Study to Learn About Variant-Adapted COVID-19 RNA Vaccine Candidate(s) in Healthy Children (clinicaltrials.gov) - P2/3 | N=4292 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Aug 2025 ➔ Jun 2026 | Trial primary completion date: Aug 2025 ➔ Jun 2026

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

COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders (clinicaltrials.gov) - P2 | N=258 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Completed ➔ Terminated; The study was closed due to continued enrollment hurdles.

Trial termination • CNS Disorders • Dermatology • Dermatomyositis • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Multiple Sclerosis • Myositis • Novel Coronavirus Disease • Pediatrics • Pemphigus Vulgaris • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza (clinicaltrials.gov) - P2 | N=1019 | Completed | Sponsor: BioNTech SE | Phase classification: P1/2 ➔ P2

Phase classification • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Safety Monitoring of Bivalent COVID-19 mRNA Vaccines Among Recipients 6 Months and Older in the United States. (PubMed, Pharmacoepidemiol Drug Saf) - "Results were consistent with published COVID-19 vaccine safety studies and support the safety profile of bivalent COVID-19 mRNA vaccines."

Journal • Cardiovascular • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Safety and Immunogenicity of Concomitant Administration and Combined Administration of Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine with or Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age. (PubMed, Vaccines (Basel)) - P2 | "Participants received concomitantly administered RSVpreF and bivalent BA.4/BA.5-adapted BNT162b2 vaccine (concomitant administration) with or without quadrivalent influenza vaccine (QIV), admixed combined RSVpreF + BNT162b2 vaccine (combined vaccine) with or without QIV, RSVpreF, BNT162b2, or QIV...No AEs leading to study withdrawal or vaccine-related SAEs were reported. Favorable safety and tolerability alongside similar immunogenicity provide support for concomitant or combined use of RSVpreF and BNT162b2, with or without QIV, to help protect older adults from these important respiratory pathogens (NCT05886777)."

Journal • Fatigue • Infectious Disease • Influenza • Novel Coronavirus Disease • Pain • Respiratory Diseases • Respiratory Syncytial Virus Infections

Indirect comparison of the relative vaccine effectiveness of mRNA-1283 vs. BNT162b2 vaccines against symptomatic COVID-19 among US adults. (PubMed, Curr Med Res Opin) - "To indirectly compare the effectiveness of mRNA-1283 and BNT162b2 against symptomatic COVID-19 among adults in the U.S. A targeted literature review was conducted to identify relevant studies comparing the mRNA-1273 and BNT162b2 bivalent vaccines. This analysis provides consistent and statistically significant evidence indicating the next-generation mRNA-1283 vaccine is more effective in preventing symptomatic COVID-19 than BNT162b2, with the largest effect in individuals aged ≥65. Consistent results across sensitivity analyses underscore the robustness of the findings, offering important evidence to inform vaccination decisions by policymakers, providers, and payers."

Journal • Infectious Disease • Novel Coronavirus Disease

Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People (clinicaltrials.gov) - P1 | N=383 | Completed | Sponsor: BioNTech SE | Active, not recruiting ➔ Completed

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

The Effectiveness of COVID-19 Vaccines During the Pre-Omicron and Omicron Periods: A Retrospective Test-Negative Case-Control Study. (PubMed, Vaccines (Basel)) - "Our study confirms that the COVID-19 vaccines protect adult patients from hospitalizations, including the subgroup ≥80 years, also during the period of the Omicron variant's predominance."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety of Simultaneous vs Sequential mRNA COVID-19 and Inactivated Influenza Vaccines: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P4 | "A total of 335 persons (mean [SD] age, 33.4 [15.1] years) were randomized (169 to the simultaneous group and 166 to the sequential group); 211 (63.0%) were female, and 255 (76.1%) received bivalent BNT162b2 mRNA COVID-19 vaccine. These findings support the option of simultaneous administration of these vaccines. ClinicalTrials.gov Identifier: NCT05028361."

Clinical • Journal • Infectious Disease • Influenza • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Comparative Effectiveness of the Bivalent (Original/Omicron BA.4/BA.5) mRNA COVID-19 Vaccines mRNA-1273.222 and BNT162b2 Bivalent in Adults with Underlying Medical Conditions in the United States. (PubMed, Vaccines (Basel)) - "Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations."

HEOR • Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases

Health characteristics associated with persistence of SARS-CoV-2 antibody responses after repeated vaccinations in older persons over time: the Doetinchem cohort study. (PubMed, Immun Ageing) - "Although older persons with comorbidities such as inflammatory and cardiometabolic diseases responded well to SARS-CoV-2 booster vaccinations, they showed a reduced persistence of these responses. This might indicate that especially these more vulnerable older persons could benefit from repeated booster vaccinations."

Journal • Infectious Disease • Inflammation • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

COMPARATIVE EFFECTIVENESS OF THE BIVALENT COVID-19 MRNA VACCINES, MRNA1273-222 AND BNT162B2, IN ADULTS WITH CHRONIC LUNG DISEASES IN THE UNITED STATES (CHEST 2024) - "In this study, the mRNA-1273.222 vaccine offered greater protection against COVID-19–related hospitalization compared with the BNT162b2 bivalent vaccine in a cohort of individuals with chronic lung diseases. CLINICAL IMPLICATIONS: This study emphasizes the importance of continuous assessment of COVID-19 vaccine formulations, ensuring optimized protection, especially among vulnerable populations, including those with chronic lung diseases."

Clinical • HEOR • Asthma • Bronchiectasis • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Interstitial Lung Disease • Novel Coronavirus Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Enhancing Omicron Sublineage Neutralization: Insights From Bivalent and Monovalent COVID-19 Booster Vaccines and Recent SARS-CoV-2 Omicron Variant Infections. (PubMed, Influenza Other Respir Viruses) - "This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS-CoV-2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Predicting herd immunity achievement: a time-series analysis of vaccination and fatality rates using 1,075 days of COVID-19 data. (PubMed, Front Public Health) - "The BNT162b2 bivalent vaccine has significantly reduced vaccine hesitancy and is linked with lower fatality rates, particularly in those aged 80 and above...Effective strategies include creating urgency, offering incentives, and prioritizing vulnerable age groups. Despite these challenges, the government should have continued to encourage vaccinations while gradually lifting COVID-19 control measures, balancing public health safety with the return to normal life, as was observed in the transition period during the latter stages of the pandemic."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and Immunogenicity of Coadministered Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine With and Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age (IDWeek 2024) - No abstract available

Clinical • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Syncytial Virus Infections

Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5-11 years: a phase 2/3, randomized, active-controlled study. (PubMed, Front Immunol) - "Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years. https://jrct.niph.go.jp/, identifier jRCT2031220665."

Clinical • Journal • New P1 trial • P2/3 data • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals (clinicaltrialsregister.eu) - P2/3 | N=1454 | Sponsor: BioNTech SE

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

Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People (clinicaltrials.gov) - P1 | N=383 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

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

Safety and Effects of an Investigational COVID-19 Vaccine as Booster in Healthy People (clinicaltrials.gov) - P1 | N=380 | Recruiting | Sponsor: BioNTech SE | Active, not recruiting ➔ Recruiting

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

Comparative effectiveness of the bivalent COVID-19 mRNA vaccines, mRNA1273-222 and BNT162b2, in immunocompromised adults in the US. (ASCO 2024) - "In this study, the mRNA-1273. 222 vaccine offered greater protection against COVID-19–related hospitalization compared with the BNT162b2 bivalent vaccine among immunocompromised individuals. This study emphasizes the importance of assessing COVID-19 vaccine formulations and optimizing protection, especially in immunocompromised adults, including those with cancer."

Clinical • HEOR • Bone Marrow Transplantation • Human Immunodeficiency Virus • Immunology • Infectious Disease • Novel Coronavirus Disease • Oncology • Primary Immunodeficiency • Respiratory Diseases • Transplantation

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds. (PubMed, J Pediatric Infect Dis Soc) - P2/3 | "These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old."

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

A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza (clinicaltrials.gov) - P1/2 | N=1019 | Completed | Sponsor: BioNTech SE | Phase classification: P2 ➔ P1/2

Phase classification • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Follow-up of Immune Response in Patients with Common Variable Immunodeficiency following SARS-CoV-2 Vaccination. (PubMed, Clin Exp Immunol) - "In this study, we evaluated the humoral and cellular immune responses after four doses of mRNA-1273 and one BNT162b2 bivalent vaccine in a cohort of patients with CVID and XLA. However, the administration of the third dose improved the number of patients with seroconversion and the intensity of the humoral response, as well as the number of patients with a positive cellular response. Finally, the administration of the fourth and fifth doses improves the antibody titer and neutralization against wild type variant, but not against the prevalent XBB1.5 variant."

Journal • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Primary Immunodeficiency • Respiratory Diseases

Reduction of adverse reactions and correlation between post-vaccination fever and specific antibody response across successive SARS-CoV-2 mRNA vaccinations. (PubMed, Vaccine X) - "This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Although vaccinees with a history of post-vaccination fever were more likely to experience fever after a subsequent dose, such recurrences were infrequent. A correlation between post-vaccination fever and increased IgG titers was identified for each vaccination, irrespective of post-vaccination fever history."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Developing variant-adapted COVID-19 vaccines to improve protection against Omicron and other recent variants: a plain language summary. (PubMed, Expert Rev Vaccines) - "SummaryWhat are variant-adapted COVID-19 vaccines?The COVID-19 vaccine developed by BioNTech and Pfizer is known as BNT162b2 (Comirnaty)...These new vaccines are called variant-adapted COVID-19 mRNA vaccines.Another company, Moderna, has also developed their own variant-adapted versions of their COVID-19 mRNA vaccine, mRNA-1273 (SpikeVax).Variant-adapted vaccines can contain parts of the variant mRNA either in addition to, or instead of, that from the original virus. Vaccines that contain mRNA from two different viruses are known as bivalent, whereas vaccines that contain mRNA from a single virus are called monovalent."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases