New Nasal Spray Influenza Vaccine for Children
(Research Supplement for R15HD109732)
Project Summary/Abstract:
Influenza is still a global public health problem for children despite a vigorous campaign for influenza
vaccination in many countries. Recent emergence of the COVID-19 can also complicate influenza in children
and make it more desirable to vaccinate young children against influenza. Influenza vaccines must be
reformulated annually because of the antigenic shift and drift of circulating influenza viral strains. However,
reformulated seasonal flu vaccines do not always match the circulating strains, and there is the ever-present
threat that avian influenza viruses may adapt for transmission in humans. Additionally, currently available
antiviral drugs against influenza are facing the twin challenges of evolved drug resistance and nonspecific
side effects. Therefore, there is an urgent need for developing novel drugs, vaccines, and combinatory
therapies against influenza virus infection.
In this proposed research, we hypothesize that a universally prophylactic and therapeutic influenza
vaccine for children can be developed through creation of a self-attenuated influenza virus (SAIV) that
expresses artificial microRNAs (amiRNAs) targeting viral and/or host gene expression that are essential for
viral replication. In order to evaluate this hypothesis, we propose the following 3 specific aims for this research:
Specific Aim 1: To evaluate the efficacy of a candidate prophylactic and therapeutic SAIV vaccine
generated by viral gene-targeted attenuation.
Specific Aim 2: To assess the efficacy of a candidate SAIV vaccine generated by host gene-targeted
attenuation.
Specific Aim 3: To produce and evaluate additional dual viral and host factor-targeted prophylactic and
therapeutic SAIV vaccines.
Our proposed SAIV vaccines developed in this research will be extensively investigated in young mouse
model of influenza infection. We anticipate that the proposed research will identify a novel and safe universal
influenza vaccine and molecular therapy that could be further developed as a therapeutic vaccine to prevent
future influenza reinfection in children. Furthermore, this research program will significantly strengthen the
research environment in Texas Tech University Health Sciences Center at El Paso, and provide research
training opportunities for graduate students, medical students, and undergraduate students, throughout the
3-year performance period.
This research supplement fund will support the diversity candidate, Ms. Alejandra Munoz, for 2 year
post-baccalaureate research training through this research program.