Immunogenic properties of RSV-B1 fusion (F) protein gene-encoding recombinant adenoviruses

• Published in: Vaccine Vol. 27; no. 40; pp. 5460 - 5471
• Main Authors: Shao, Hsiao-Yun, Yu, Shu-Ling, Sia, Charles, Chen, Yana, Chitra, Ebenezer, Chen, I-Hua, Venkatesan, Nandini, Leng, Chih-Hsiang, Chong, Pele, Chow, Yen-Hung
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 04.09.2009; Elsevier; Elsevier Limited
• Subjects: Adenoviridae - genetics; Adenoviridae - immunology; Adenovirus; Adenoviruses; Allergy and Immunology; Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Applied microbiology; Biological and medical sciences; Body weight; CD4-Positive T-Lymphocytes - immunology; Cell Line; Cross Reactions; Cytokines; Cytokines - immunology; Ear diseases; Experiments; Female; Fundamental and applied biological sciences. Psychology; Fusion protein; Humans; Immune system; Immunization; Immunogenicity; Infections; Laboratory animals; Load distribution; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Neutralization Tests; Proteins; Respiratory syncytia virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - immunology; Spleen - cytology; Spleen - immunology; Studies; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Fusion Proteins - genetics; Viral Fusion Proteins - immunology; Viral infections; Viral Load; Virology; Respiratory syncytia virus; Fusion protein; Adenoviruses; Virus; Adenoviridae; Immunogenicity; Recombinant protein; Hybrid gene
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.07.004

Abstract Two recombinant adenoviruses designated rAd-F0ΔTM and rAd-F0 carrying the transmembrane truncated and full length of the F gene of the RSV-B1 strain, respectively, were engineered. Comparative immunogenicity studies in BALB/c mice showed that each vector was capable of inducing RSV-B1-specific antibodies that cross-reacted with the RSV-long and RSV-A2 viruses. The anti-RSV-B1 antibodies were neutralizing, and exhibited strong cross-neutralizing activity against the RSV-long and RSV-A2 isolates as well. Analysis of the cellular responses revealed that animals immunized with rAd-F0ΔTM and rAd-F0 elicited CD4+ T-cell responses of the Th1 and Th2 phenotypes, as well as F protein-specific CTLs. Production of Th2 cytokines (IL-4, IL-5 and IL-13) by splenocytes of the rAd-F0ΔTM and rAd-F0 immunized mice was markedly lower than those released by animals administered with heat-inactivated RSV-B1 (HIRSV-B1). Comparison of the overall humoral and cellular responses suggests that rAd-F0ΔTM is significantly more immunogenic than rAd-F0. The anti-viral immunity generated by both recombinant adenovirus vectors has conferred protection against live RSV-B1 challenge as judged by the lower viral load recovered in the lungs, a faster rate of recovery of body weight loss, and a lower count of eosinophils as compared to eosinophilia in mice immunized with HIRSV-B1. Results from these studies suggest that rAd-F0ΔTM or rAd-F0 possess immunogenic properties that meet the requirements expected from potential RSV vaccine candidates.