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, Young-Tae; Ko, Eun-Ju; Kim, Ki-Hye et al. (2017) Cellular Immune Correlates Preventing Disease Against Respiratory Syncytial Virus by Vaccination with Virus-Like Nanoparticles Carrying Fusion Proteins. J Biomed Nanotechnol 13:84-98
Gangadhara, Sailaja; Kwon, Young-Man; Jeeva, Subbiah et al. (2017) Vaccination with Combination DNA and Virus-Like Particles Enhances Humoral and Cellular Immune Responses upon Boost with Recombinant Modified Vaccinia Virus Ankara Expressing Human Immunodeficiency Virus Envelope Proteins. Vaccines (Basel) 5:
Ko, Eun-Ju; Lee, Young-Tae; Kim, Ki-Hye et al. (2017) Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine. J Immunol 198:279-291
Kim, Yu-Jin; Ko, Eun-Ju; Kim, Min-Chul et al. (2017) Roles of antibodies to influenza A virus hemagglutinin, neuraminidase, and M2e in conferring cross protection. Biochem Biophys Res Commun 493:393-398
Kim, Min-Chul; Lee, Yu-Na; Kim, Yu-Jin et al. (2017) Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate. Antiviral Res 148:43-52
Jung, Yu-Jin; Lee, Young-Tae; Ngo, Vu Le et al. (2017) Heat-killed Lactobacillus casei confers broad protection against influenza A virus primary infection and develops heterosubtypic immunity against future secondary infection. Sci Rep 7:17360
Lee, Young-Tae; Ko, Eun-Ju; Lee, Youri et al. (2016) CD47 Plays a Role as a Negative Regulator in Inducing Protective Immune Responses to Vaccination against Influenza Virus. J Virol 90:6746-58
Quan, Fu-Shi; Lee, Young-Tae; Kim, Ki-Hye et al. (2016) Progress in developing virus-like particle influenza vaccines. Expert Rev Vaccines 15:1281-93
Ko, Eun-Ju; Lee, Young-Tae; Kim, Ki-Hye et al. (2016) Effects of MF59 Adjuvant on Induction of Isotype-Switched IgG Antibodies and Protection after Immunization with T-Dependent Influenza Virus Vaccine in the Absence of CD4+ T Cells. J Virol 90:6976-88
Music, Nedzad; Reber, Adrian J; Kim, Min-Chul et al. (2016) Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets. Vaccine 34:466-473

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