Virus-like particles (VLPs) provide great potential to develop future vaccines against highly pathogenic viral pathogens. VLPs mimic the virus in structure and morphology, but are non-infectious, featuring a high safety profile. The goal of our proposed project is to develop vaccine technology based on recombinant VLPs. Respiratory syncytial virus (RSV) and influenza virus are important respiratory viral pathogens. There is no licensed vaccine against RSV. There are 9 times more deaths by RSV than those by influenza among young infants. The fact that licensed RSV drugs are based on antibodies highly supports the possibility to develop an effective RSV vaccine. We have developed RSV VLP vaccines that are proven to be effective in preventing RSV enhanced disease from recent feasibility studies. However, RSV VLP vaccine technology is in an early stage of development and much study is needed to provide sufficient preclinical efficacy data of RSV VLP vaccines. We hypothesize that RSV VLP vaccines developed in our feasibility studies will be highly effective in inducing protective immunity against RSV. In the specific aim 1, we will focus on obtaining sufficient proof-of-concept efficacy data of RSV VLP vaccines as well as testing long-term immunity and non-needle delivery technologies (intranasal, microneedle skin, and oral vaccination). As for aim 2, we will develop antigen targeting vaccine adjuvant systems by using molecularly adjuvanted VLP technology and test licensed adjuvants. Also, utilizing VLP vaccine technology, we have developed a promising universal influenza VLP vaccine and obtained sufficient proof-of-concept efficacy data, which is expected to significantly improve the current egg-substrate based influenza vaccines. In the aim 3, we will extend the preclinical efficacy tests of VLP vaccines to cotton rats (RSV VLPs) and ferrets (novel universal influenza VLPs). VLP vaccines proposed in this application will provide an excellent system to prove VLP vaccine technologies which are also applicable to other biodefense pathogens.

Public Health Relevance

Recombinant virus-like particles are considered as a promising new technology to develop future vaccines against viral pathogens such as influenza and Respiratory Syncytial virus, both of which continue to cause public health problems. Therefore, development of virus-like particle vaccine technology including novel adjuvants and non-needle vaccine delivery will have a significant impact on developing new vaccines, and thus improving the public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI105170-02
Application #
8603845
Study Section
Special Emphasis Panel (ZAI1-SM-M (J1))
Program Officer
Salomon, Rachelle
Project Start
2013-01-15
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$653,700
Indirect Cost
$137,312
Name
Georgia State University
Department
Miscellaneous
Type
Organized Research Units
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul et al. (2015) Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease. Antiviral Res 115:8-Jan
Ko, Eun-Ju; Kwon, Young-Man; Lee, Jong Seok et al. (2015) Virus-like nanoparticle and DNA vaccination confers protection against respiratory syncytial virus by modulating innate and adaptive immune cells. Nanomedicine 11:99-108
Tang, Yinghua; Lu, Jihu; Wu, Peipei et al. (2014) Inactivated vaccine with adjuvants consisting of pattern recognition receptor agonists confers protection against avian influenza viruses in chickens. Vet Microbiol 172:120-8
Kwon, Young-Man; Hwang, Hye Suk; Lee, Jong Seok et al. (2014) Maternal antibodies by passive immunization with formalin inactivated respiratory syncytial virus confer protection without vaccine-enhanced disease. Antiviral Res 104:1-6
Lee, Sujin; Quan, Fu-Shi; Kwon, Youngman et al. (2014) Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins. Antiviral Res 111:129-35
Lee, Jong Seok; Ko, Eun-Ju; Hwang, Hye Suk et al. (2014) Antiviral activity of ginseng extract against respiratory syncytial virus infection. Int J Mol Med 34:183-90
Lee, Yu-Na; Lee, Young-Tae; Kim, Min-Chul et al. (2014) Fc receptor is not required for inducing antibodies but plays a critical role in conferring protection after influenza M2 vaccination. Immunology 143:300-9
Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi et al. (2014) Cutaneous immunization: an evolving paradigm in influenza vaccines. Expert Opin Drug Deliv 11:615-27
Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae et al. (2014) AS04-adjuvanted virus-like particles containing multiple M2 extracellular domains of influenza virus confer improved protection. Vaccine 32:4578-85
Lee, Jong Seok; Cho, Min Kyoung; Hwang, Hye Suk et al. (2014) Ginseng diminishes lung disease in mice immunized with formalin-inactivated respiratory syncytial virus after challenge by modulating host immune responses. J Interferon Cytokine Res 34:902-14

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