PMID:22623776

Citation	Qiu, H, Li, X, Tian, X, Zhou, Z, Xing, K, Li, H, Tang, N, Liu, W, Bai, P and Zhou, R (2012) Serotype-specific neutralizing antibody epitopes of human adenovirus type 3 (HAdV-3) and HAdV-7 reside in multiple hexon hypervariable regions. J. Virol. 86:7964-75
Abstract	Human adenovirus types 3 and 7 (HAdV-3 and HAdV-7) occur epidemically and contribute greatly to respiratory diseases, but there is no currently available licensed recombinant HAdV-3/HAdV-7 bivalent vaccine. Identification of serotype-specific neutralizing antibody (NAb) epitopes for HAdV-3 and HAdV-7 will be beneficial for development of recombinant HAdV-3/HAdV-7 bivalent vaccines. In this study, four NAb epitopes within hexon hypervariable regions (HVRs) were predicted for HAdV-3 and HAdV-7, respectively, by using bioinformatics. Eight hexon chimeric adenovirus vectors with the alternation of only one predicted neutralizing epitope were constructed. Further in vitro and in vivo neutralization assays indicated that E2 (residing in HVR2) and E3 (residing in HVR5) are NAb epitopes for HAdV-7, and E3 plays a more important role in generating NAb responses. Cross-neutralization assays indicated that all four predicted epitopes, R1 to R4, are NAb epitopes for HAdV-3, and R1 (residing in HVR1) plays the most important role in generating NAb responses. Humoral immune responses elicited by the recombinant rAdH7R1 (containing the R1 epitope) were significantly and durably suppressed by HAdV-3-specific NAbs. Surprisingly, the rAdΔE3GFP-specific neutralizing epitope responses induced by rAdMHE3 (R3 replaced by E3) and rAdMHE4 (R4 replaced by E4) were weaker than those of rAdMHE1 (R1 replaced by E1) or rAdMHE2 (R2 relaced by E2) in vitro and in vivo. Furthermore, rAdMHE4 replicated more slowly in HEp-2 cells, and the final yield was about 10-fold lower than that of rAdΔE3GFP. The current findings contribute not only to the development of new adenovirus vaccine candidates, but also to the construction of new gene delivery vectors.
Links	PubMed PMC3421688 Online version:10.1128/JVI.07076-11
Keywords	Adenovirus Infections, Human/genetics; Adenovirus Infections, Human/immunology; Adenovirus Infections, Human/prevention & control; Adenoviruses, Human/genetics; Adenoviruses, Human/immunology; Animals; Antibodies, Neutralizing/immunology; Antibodies, Viral/immunology; Capsid Proteins/genetics; Capsid Proteins/immunology; Epitopes/genetics; Epitopes/immunology; Female; Gene Transfer Techniques; Mice; Mice, Inbred BALB C; Species Specificity; Viral Vaccines/genetics; Viral Vaccines/immunology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ADE02:PRO		GO:0097282: immunoglobulin-mediated neutralization	ECO:0000314:		P		fig 4 shows neutralization	complete

References

See Help:References for how to manage references in GONUTS.