Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

The goal of the Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) study is to conduct, on a yearly basis, direct comparisons of immunogenicity and reactogenicity of the most recent versions of FDA-approved vaccines for COVID-19 and/or influenza. Studies will be conducted on individuals that are FDA eligible to receive these vaccines and do not have a medical condition that severely impairs their immune system. For 2025, the study will directly compare the immunogenicity and reactogenicity of the 2025 Novavax recombinant COVID-19 vaccine with the 2025 Pfizer/BioNTech mRNA COVID-19 vaccine.

Inclusion criteria

• 18-79 years old
• Have a history of any of the following risk factors for severe COVID:

• Asthma
• Physical inactivity (defined as <150 mins of moderate activity per week or <75 mins of vigorous activity per week)
• HIV with CD4 count ≥ 500 cells/ul
• Current or prior smoker
• Depression or other mood disorder
• Schizophrenia spectrum disorder
• Cerebrovascular disease
• Heart failure
• Coronary artery disease
• Cardiomyopathy
• Pulmonary embolism
• Pulmonary hypertension
• Cystic fibrosis
• Bronchiectasis
• Chronic obstructive pulmonary disease
• Interstitial Lung Disease
• Stage I or II chronic kidney disease
• Stage 1 defined as normal GFR (> 90) but with other signs of kidney damage such as proteinuria or hematuria
• Stage 2 defined as having a glomerular filtration rate (GFR) of 60 - 89 ml/min/1.73m2
• Gestational diabetes
• Type 1 diabetes with most recent HgbA1C < 7.5%
• Type 2 diabetes with most recent HgbA1C < 7.5%
• Obesity with BMI ≥ 30 and < 40
• Liver disease without cirrhosis and with liver enzyme levels
• (AST and ALT) no greater than three times the upper limit of normal
• Military Health System beneficiary and DEERS eligible
• Willing to be randomized to receive either the Novavax COVID-19 vaccine or the mRNA Pfizer-BioNTech COVID-19 vaccine
• Will be able to return for a clinic visit in approximately 30 days and be able to follow-up online for the next 9 months.

Exclusion criteria

• History of severe allergy or severe adverse reaction such as myocardial inflammation to any component of the mRNA COVID-19 vaccines or the Novavax recombinant COVID-19 vaccine
• Received a COVID-19 vaccine in the last 3 months.
• Tested positive for COVID-19 in the past 3 months.

• Presence of fever, cough, chills, shortness of breath, runny nose, or sore throat today on day of screening/enrollment visit.
• Active use of immune modulating medications.

• Defined as active use of chronic immune modulating medications such as systemic corticosteroids at a dose equivalence of 20 mg prednisone or greater daily for over one month, chemotherapy, cytokine inhibitors, or agents that reduce T cell or B cell numbers or function.
• Diagnosed with immunocompromised stated.

• Defined as: presence of a disease that is actively causing severe immune suppression or history of prior splenectomy (removal of spleen).
• Diabetes with the most recent HgbA1C ≥ 7.5.
• Stage III or greater chronic kidney disease

• Defined as estimated glomerular filtration rate < 60 ml/min/1.73m2)
• Obesity with a BMI ≥ 40
• HIV with a CD4 cell count < 500 cells/ul
• History of solid organ or bone marrow transplant.
• Active malignancy

• Defined as any cancer that is currently being treated or has shown evidence of progression within the past year.
• Chronic liver disease with compensated or decompensated cirrhosis, or liver enzyme levels (AST or ALT) greater than three times the upper limit of normal.