Immunogenic properties of RSV-B1 fusion (F) protein gene-encoding recombinant adenoviruses.
Two recombinant adenoviruses designated rAd-F0DeltaTM 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-F0DeltaTM 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-F0DeltaTM 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-F0DeltaTM 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-F0DeltaTM or rAd-F0 possess immunogenic properties that meet the requirements expected from potential RSV vaccine candidates.
Shao
Hsiao-Yun
HY
Vaccine R&D Center, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan, ROC.
Yu
Shu-Ling
SL
Sia
Charles
C
Chen
Yana
Y
Chitra
Ebenezer
E
Chen
I-Hua
IH
Venkatesan
Nandini
N
Leng
Chih-Hsiang
CH
Chong
Pele
P
Chow
Yen-Hung
YH
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D000914:Antibodies, Viral; D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins