Health Sciences Program Student Theses, Dissertations and Capstones

Document Type

Dissertation - NSU Access Only

Degree Name

Doctor of Philosophy (PhD) in Health Science

Copyright Statement

All rights reserved. This publication is intended for use solely by faculty, students, and staff of Nova Southeastern University. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.

Department

College of Health Care Sciences – Health Science Department

First Advisor

Peter Holub

Date of original Performance / Presentation

January 2022

Publication Date / Copyright Date

1-1-2022

Abstract

Identification of key factors associated with impaired or imbalanced immune responses to influenza vaccines represents an important gap in influenza vaccinology. Utilizing a retrospective quantitative correlational design, this investigator researched influenza vaccine responsiveness in a cohort of 50 healthy adult donors via the fully human, in vitro immune (Modular Immune In Vitro Construct (MIMIC©) platform. This dissertation study was conducted using de-identified human influenza vaccine immunogenicity data extracted from the 2007 archival blood database belonging to and maintained at VaxDesign Corporation, 2501 Discovery Drive, Suite 300, Orlando, FL 32826. Donors were screened and classified as non-responders or responders based on functional antibody response to influenza A/H1/Michigan/45/2015. While hemagglutinin (HA) antibody titers are the standard correlate of protection for influenza, this investigator also evaluated antibody responses to neuraminidase (NA) and CD4 T cell responses to multiple influenza antigens. Donors were stimulated with two different commercial influenza vaccines formulated with 2018/2019 Northern Hemisphere strains and manufactured using either recombinant cell technology or egg-based production. Results showed that fluzone egg-based vaccine induced statistically higher antibody responses and flublok recombinant vaccine induced higher cellular responses. Pre-existing sera antibody levels were not correlated with vaccine-induced immune responses. Principal component analysis identified clustering of circulating cytotoxic T cells (CTL) with antibody and cellular immune responses while principal regression analysis indicated that CD25 expression on activated T cells is an important factor in influenza vaccine immune responses. This investigator has identified novel potential biomarkers of influenza vaccine responsiveness and provided human immunological data to inform influenza vaccine recommendations in adults 18 to 49.

Disciplines

Medicine and Health Sciences

Keywords

biomarker; epidemic; influenza; pandemic; universal; vaccines

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