1. Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates
- Author
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Deborah H. Fuller, Michael G. Katze, Juliet Morrison, Kelly Stefano-Cole, Shulin Qin, Karen M. Duus, James T. Fuller, Jolie A. Leonard, Todd A. Reinhart, Debra Bratt, Merika Treants Koday, Michael Koday, Robert D. Murnane, Paul V. Munson, Adriana Forero, Amy L. Hartman, Ilhem Messaoudi, and Krammer, Florian
- Subjects
0301 basic medicine ,and promotion of well-being ,Viral Diseases ,Physiology ,T-Lymphocytes ,lcsh:Medicine ,Antibody Response ,Monkeys ,medicine.disease_cause ,DNA vaccination ,Biochemistry ,White Blood Cells ,0302 clinical medicine ,Influenza A Virus, H1N1 Subtype ,Animal Cells ,Immune Physiology ,Influenza A virus ,Influenza A Virus ,Medicine and Health Sciences ,Vaccines, DNA ,030212 general & internal medicine ,Enzyme-Linked Immunoassays ,Neutralizing antibody ,lcsh:Science ,Neutralizing ,Immune Response ,Mammals ,Vaccines ,Multidisciplinary ,Immune System Proteins ,biology ,T Cells ,Immunogenicity ,Antibody titer ,Eukaryota ,3. Good health ,Infectious Diseases ,3.4 Vaccines ,5.1 Pharmaceuticals ,Influenza Vaccines ,Vertebrates ,Pneumonia & Influenza ,Vaccination and immunization ,Development of treatments and therapeutic interventions ,Cellular Types ,Infection ,Viral load ,Macaque ,Biotechnology ,Research Article ,Primates ,Infectious Disease Control ,General Science & Technology ,Immune Cells ,Immunology ,Heterologous ,Cross Reactions ,Research and Analysis Methods ,Virus ,Antibodies ,Vaccine Related ,03 medical and health sciences ,Biodefense ,MD Multidisciplinary ,Old World monkeys ,medicine ,Animals ,H1N1 Subtype ,Vaccine Related (AIDS) ,Immunoassays ,Preventive medicine ,Blood Cells ,Biology and life sciences ,Prevention ,lcsh:R ,Organisms ,Proteins ,DNA ,Cell Biology ,Prevention of disease and conditions ,Virology ,Antibodies, Neutralizing ,Influenza ,Macaca fascicularis ,030104 developmental biology ,Emerging Infectious Diseases ,Public and occupational health ,Amniotes ,biology.protein ,Immunologic Techniques ,Immunization ,lcsh:Q - Abstract
Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA) universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.
- Published
- 2017