Viruslike Particles Encapsidating Respiratory Syncytial Virus M and M2 Proteins Induce Robust T Cell Responses
- Schwarz, Benjamin [ Indiana Univ, Dept Chem, 800 East Kirkwood Ave, Bloomington, IN 47405 USA ]
- Morabito, Kaitlyn M [ NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA ] [ Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA ]
- Ruckwardt, Tracy J [ NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA ]
- Patterson, Dustin P [ Univ Texas Tyler, Dept Chem & Biochem, 3900 Univ Blvd, Tyler, TX 75799 USA ]
- Avera, John [ Indiana Univ, Dept Chem, 800 East Kirkwood Ave, Bloomington, IN 47405 USA ]
- Miettinen, Heini M [ Montana State University: Microbiology & Cell Biology ]
- Graham, Barney S [ NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA ]
- Douglas, Trevor [ Montana State University: Chemistry & Biochemistry ] [ Indiana Univ, Dept Chem, 800 East Kirkwood Ave, Bloomington, IN 47405 USA ]
Subunit vaccines provide a safe, focused alternative to conventional vaccines. However, these vaccines often require significant adjuvants and are particularly hard to target toward cytotoxic T lymphocyte (CTL) immunity. Viruslike particles (VLPs) provide biomaterial scaffolds with pathogen-like polyvalent structures making them useful platforms for biomimetic antigen delivery to the immune system. Encapsidation of antigens within VLPs has been shown to enhance antigen availability for CD8 T cell responses. Here, we examine the potential to generate complex responses to multiple subunit antigens localized within the same VLP particle. Two proteins of respiratory syncytial virus (RSV) with well-characterized CD8 T cell responses, the matrix (M) and matrix 2 (M2) proteins, were successfully coencapsidated within the P22 VLP. Upon intranasal administration in mice, the particles stimulated CD8 T cell memory responses against both antigens. In addition, vaccination elicited tissue-resident T cell populations. Upon subsequent RSV challenge, P22-M/M2-treated mice displayed significantly reduced lung viral titers. This demonstrates the utility of the P22 VLP in directing immune responses to multiple encapsidated viral antigens, demonstrating the potential of this technology to facilitate immunity to multiple targets simultaneously.