Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model

• Published in: Human vaccines & immunotherapeutics Vol. 10; no. 3; pp. 615 - 622
• Main Authors: Passmore, Crystal, Makidon, Paul E, O'Konek, Jessica J, Zahn, Joseph A, Pannu, Jessie, Hamouda, Tarek, Bitko, Vira, Myc, Andrzej, Lukacs, Nicolas W, Fattom, Ali, Baker, Jr, James R
• Format: Journal Article
• Language: English
• Published: United States 2014
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Animals; Antibodies, Viral - analysis; Antibodies, Viral - blood; Blood - immunology; Disease Models, Animal; Emulsions - administration & dosage; Female; Immunity, Mucosal; Immunization - methods; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - administration & dosage; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Viruses - immunology; Respiratory Syncytial Viruses - isolation & purification; Th2 Cells - immunology; Treatment Outcome; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Viral Fusion Proteins - immunology; RSV vaccine; intranasal vaccination; F-protein; nanoemulsion; adjuvant
• ISSN: 2164-5515; 2164-554X
• DOI: 10.4161/hv.27383

Respiratory Syncytial Virus (RSV) is a ubiquitous virus that infects almost all people by age two and is a major source of respiratory illness in infants, the elderly and others with compromised immune systems. Currently there is no available vaccine. Prior efforts using formalin-inactivated RSV (FI-RSV) were associated with enhanced respiratory disease upon viral exposure following clinical vaccine trials. Several researchers and pharmaceutical companies have utilized vector-associated live attenuated RSV vaccines in pre-clinical and clinical studies. Another attractive approach, however, is a subunit vaccine which would be easier to produce and quality control. Our group has previously demonstrated in a murine model of infection that intranasal immunization with nanoemulsion-inactivated and adjuvanted RSV induces humoral and cellular immune responses, resulting in protection against RSV infection. The present studies characterize the immune responses elicited by intranasal RSV F protein adjuvanted with nanoemulsion. Intranasal application of nanoemulsion adjuvanted F protein induced a rapid and robust systemic and mucosal antibody response, as well as protection against subsequent RSV challenge. Importantly, RSV challenge in immunized animals did not elicit airway hyper-reactivity, a Th2-skewed immune response or immunopathology associated with hypersensitivity reactions with formalin-inactivated vaccine. These results suggest that RSV F protein adjuvanted with nanoemulsion may be a good mucosal vaccine candidate. Formulating RSV F protein in nanoemulsion creates a well-defined and well-controlled vaccine that can be delivered intranasally to induce T cell mediated immunity without inducing enhanced disease associated with the mouse model of FI-RSV vaccination and infection.