The goal of this pragmatic embedded open-label, 2 x 2 factorial phase II randomized controlled trial is to evaluate strategies to improve COVID-19 booster and influenza vaccine immunogenicity in people living with immunocompromising conditions (PLIC).
The main questions it aims to answer are:
1. Is co-administration of seasonal inactivated influenza vaccine (IIV) with the most up-to-date recommended COVID-19 booster dose non-inferior in inducing a 1-month peak protective humoral response against COVID-19, compared to a strategy of sequential administration of COVID-19 booster dose followed by seasonal IIV given one month later? 2. Is the administration of the most up-to-date recommended COVID-19 booster doses at 3-month intervals superior at maintaining a longer term protective humoral immune response, compared to booster doses administered at 6-month intervals?
Researchers will compare (1) COVID-19 and Influenza vaccines administered at Day 0 + COVID-19 Booster at a 3-month interval, (2) COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 + COVID-19 Booster at a 3-month interval, (3) COVID-19 and Influenza vaccines administered at Day 0 + COVID-19 Booster at a 6-month interval, and (4) COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 + COVID-19 Booster at a 6-month interval to see if median neutralization capacity of patient sera is non-inferior in the co- vs. sequential administration arms at 1-month after the initial COVID-19 booster and superior in the 3-month interval arms vs. the 6-month interval arms at 12 months after the initial COVID-19 booster. These outcomes will also be compared at 2-months for question 1 and 6-months for question 2.
People living with immunocompromising conditions who take part in the trial will have blood samples drawn to verify immune response, be monitored for changes in clinical events and therapies, and complete questionnaires to verify adverse effects, quality of life and economic impact.
None
Annual vaccination against influenza < 6 months ago
life-threatening reaction any component of the IIV or COVID-19 vaccines
Guillain-Barre syndrome or myocarditis within 6 weeks of a previous influenza or COVID-19 vaccination
Contraindication to intramuscular vaccines such as bleeding disorder, severe thrombocytopenia, etc; iii. Receiving intravenous immunoglobulins; iv. Have underlying primary inborn errors of immunity; v. Receiving chemotherapy such as cyclophosphamide < 6-months ago; vi. Unable to provide informed consent
Factorial
Inactivated influenza vaccine (IIV) at baseline
Biological/VaccineNational Advisory Committee on Immunization (NACI) recommended seasonal inactivated influenza vaccine for moderate to severely immunocompromised patients by age at baseline
COVID-19 Vaccines at a 3-month interval
Biological/VaccineUpdated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 3-month interval
Inactivated influenza vaccine at Month 1
Biological/VaccineNational Advisory Committee on Immunization (NACI) recommended seasonal inactivated influenza vaccine for moderate to severely immunocompromised patients by age 1-month following initial COVID-19 booster
COVID-19 Vaccines at a 6-month interval
Biological/VaccineUpdated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 6-month interval
Median neutralization capacity against prevalent SARS-CoV-2 variant
Median neutralization capacity of patient sera/plasma from each group, as measured by half maximal inhibitory dilution (ID50) against the prevalent SARS-CoV-2 variant circulating at time of measurement. For objective 1, this outcome will be compared between the co- vs. sequential administration arms at 1-month (T1) after the COVID-19 booster (peak humoral response). This outcome will also be compared at 2-months (T2). For objective 2, this outcome will be compared 12-months (T12) after the first COVID-19 booster between participants who have received COVID-19 boosters at 0, 3, 6 and 9 months (3-month interval arm) vs. those who received COVID-19 booster doses at 0 and 6-months (6-month interval arm). This outcome will also be compared at 6-months (T6).
Median neutralization capacity against ancestral and SARS-CoV-2 variant in vaccine
D50 against the SARS-CoV-2 variant included in the vaccine with measurements against the ancestral variant serving as a reference
Anti-Spike and anti-Nucleocapsid concentrations
Concentration of anti-Spike (response to vaccines) and anti-Nucleocapsid (SARS-CoV-2 infection)
IgA, and IgM antibody concentration
IgA, and IgM antibody concentration against SARS-CoV-2 and IgG1 to 4 subtypes (in a subset of participants)
Hemagglutination inhibition (HI) response
Hemagglutination inhibition (HI) response for each influenza strain in the vaccine
Adverse reactions to the vaccines
Adverse reactions to the vaccines will be verified by monitoring participants for a period of 30 mins following vaccine administration. Also, self-reported adverse events (Reactogenicity) and their severity will be recorded by patients using a diary for a period of 1-week following each vaccine administration.
Evidence of immune activation
Evidence of immune activation (e.g., rheumatological or inflammatory bowel disease flares, allograft rejection, or development of donor-specific antibodies)
SARS-CoV-2 infections
Evidence of SARS-CoV-2 infections
Influenza infections
Evidence of Influenza infections
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McGill University Health Centre/Research Institute of the McGill University Health Centre
Lead sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborator
