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A combined carrier-adjuvant system of peptide nanofibers and toll-like receptor agonists potentiates robust CD8+ T cell responses
Affiliation:1. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-0436, United States;2. Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0436, United States;3. Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0436, United States;4. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-0436, United States;1. Real-time Syndromic Surveillance Team, National Infection Service, Public Health England, 1st Floor, 5 St Philips Place, Birmingham B3 2PW, United Kingdom;2. The Phoenix Partnership (TPP), TPP House, 129 Low Lane, Horsforth, Leeds LS18 5PX, United Kingdom;3. Public Health England West Midlands, 6th Floor, 5 St Philips Place, Birmingham B3 2PW, United Kingdom;4. Immunisation, Hepatitis and Blood Safety Department, National Infection Service, Public Health England, 61 Colindale Avenue, London NW9 5EQ, United Kingdom;5. Royal College of General Practitioners Research and Surveillance Centre, University of Surrey, Section of Clinical Medicine and Ageing, Guildford, Surrey GU2 7XH, United Kingdom;1. Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, United States;2. Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, United States;3. Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, United States;1. Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States;2. Baylor Scott & White Health, Texas A&M College of Medicine, Temple, TX, United States;3. Marshfield Clinic Research Institute, Marshfield, WI, United States;4. University of Michigan, Ann Arbor, MI, United States;5. University of Pittsburgh, Pittsburgh, PA, United States;6. Centers for Disease Control and Prevention, Atlanta, GA, United States;1. Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), United States;2. HIV Incidence and Case Surveillance Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC), United States;3. Flexcare Medical Staffing, Roseville, CA, United States;1. The Louis Stokes VA Medical Center, Cleveland, OH, USA;2. Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, OH, USA;3. Department of Medicine, MetroHealth Medical Center, Case Western Reserve, Cleveland, OH, USA;4. Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA;5. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, USA;6. Harvard T.H. Chan School of Public Health, Boston, MA, USA
Abstract:
Improving CD8+ T cell responses activated by subunit vaccination is crucial for improving vaccine efficacy and safety. Here we report a carrier-adjuvant system composed of self-assembling peptide nanofibers presenting an immunodominant antigen from herpes simplex virus (HSV) and toll-like receptor (TLR) agonists that induces robust effector and memory CD8+ T cell responses in mice. The effector function of vaccine-induced CD8+ T cells was influenced by the type of TLR agonist. The use of CpG (TLR9 agonist) resulted in significantly greater specific in vivo cytotoxicity and trended towards more cells producing both IFN-γ and TNF-α compared to gardiquimod (TLR7 agonist). Prime-boost immunization with peptide nanofibers combined with either adjuvant resulted in development of HSV-specific CD8+ memory T cells further demonstrating the capability of the carrier-adjuvant system to induce strong HSV-specific CD8+ T cell responses. Inclusion of peptide epitope-nanofibers in protein-based subunit vaccines should increase the functional spectrum of the vaccine-elicited immune response and protection.
Keywords:TLR agonist adjuvants  CD8+ T cell  HSV-2  Peptide nanofiber  Vaccine
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