Systems Investigation of Vaccine Responses in Aging and Frailty

There are two vaccines currently approved for use in adults age 65 and greater: a high-dose (HD) influenza vaccine (Fluzone High-Dose) that contains 4 times the hemagglutinin dose found in the standard vaccine, and a standard-dose (SD) vaccine containing the proprietary MF59 adjuvant (Fluad). Both vaccines give significantly highly antibody responses to influenza in older adults. This study will directly compare the HD and SD vaccines in nursing home residents, the population of older adults most vulnerable to influenza outbreaks and morbidity and mortality. It will comprehensively study the innate and adaptive response to vaccination, as well as elucidate transcriptomic and proteomic signatures of vaccine response.

This is a randomized, open label study comparing the two vaccines currently approved for use in adults age ≥ 65 years: the high-dose influenza vaccine and the MF59 adjuvanted standard-dose vaccine, both quadrivalent. The young group will be comprised of individuals 21-30 years of age, and the older cohorts will consist of nursing home residents ≥65 years. Participants will also be evaluated for evidence of influenza-like illness (ILI). ILI is defined to include clinical presentation in older adults: by the presence of either two respiratory symptoms (cough, sore throat, shortness of breath, and nasal stuffiness) or one respiratory and one systemic symptom (headache, malaise, temperature \>99° F, report of feverishness and muscle aches, or altered mental status). Diagnoses of influenza will be confirmed using a real-time polymerase chain reaction (PCR) test on a nasopharyngeal (NP) swab specimen done by the hospital Virology Laboratory and facilitated by the participating medical directors.

Although this is neither an efficacy or effectiveness study, participants will be randomized 1:1 to either the high-dose influenza vaccine or the MF59 vaccine within age strata. This will ensure a non-biased allocation of the two vaccines and attempts to balance participant characteristics within age strata.

Participants age 21-30 years will receive the standard dose Fluad

Biological: Fluad

Participants age 21-30 years will receive the high dose Fluzone

Biological: Fluzone

Participants age ≥65 years will receive standard dose Fluad

Biological: Fluad

Participants age ≥65 years will receive high dose Fluzone

Biological: Fluzone

Fluzone High-Dose 0.7 ml intramuscular injection, standard as recommended by manufacturer

Fluad Quadrivalent, MF59 adjuvanted 0.5 ml intramuscular injection, standard as recommended by manufacturer

Plazo: Baseline and at Day 2, 7, and 28 post-vaccine

Measurement of IL-6 production in monocytes via flow cytometry

Plazo: Baseline and Day 28

HAI titers levels in blood measured prior to and at day 28 post-vaccine

Plazo: At Baseline, Day 2, Day 7, Day 28 and Day 70

RNA-seq analysis of RNA derived from peripheral blood mononuclear cells (PBMCs) and platelet-rich plasma (PRP)

Plazo: At Baseline, Day 2, Day 7, Day 28 and Day 70

Analysis of protein expression using Mass Spectrometry in plasma

Plazo: At Baseline, Day 2, Day 7, Day 28 and Day 70

Analyses will include intracellular production of cytokines including IL-10 and TNF-alpha in monocyte populations from PBMCs and expression of platelet activation markers such as CD63 and P-selectin on platelets. The effects of ex vivo Toll-like Receptor stimulation on these parameters will also be assessed.

Plazo: At Baseline, Day 2, Day 7, Day 28 and Day 70

This will include analysis of number and proportion of antibody-secreting cells post-vaccine, and analyses of T cells following ex vivo stimulation of PBMCs with influenza hemagglutinins.

Systems Investigation of Vaccine Responses in Aging and Frailty