Kinetics of protective antibodies are determined by the viral surface antigen.
Delayed and weak virus neutralizing antibody (nAb) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. Using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. Swapping the glycoproteins (GPs) of lymphocytic choriomeningitis virus (LCMV, naturally persisting, noncytolytic, inefficient nAb inducer) and vesicular stomatitis virus (VSV, nonpersisting, cytolytic, potent nAb inducer) transferred the only target of nAb's from either virus to the other. We analyzed the nAb response to each of the 2 recombinant and parent viruses in infected mice and found that nAb kinetics were solely determined by the viral surface GP and not by the virus backbone. Moreover, the slowly and poorly nAb-triggering LCMV virion was a potent immunogenic matrix for the more antigenic VSV-GP. These findings indicate that the viral GP determines nAb kinetics largely independently of the specific viral infection context. They further suggest that structural features of viral GPs or coevolutionary adaptation of the virus's GP to the host's naive B cell repertoire, or both, may critically limit nAb kinetics and improvement of vaccine efficacy.
Pinschewer
Daniel D
DD
Institute of Experimental Immunology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland. pinschi@pathol.unizh.ch
Perez
Mar
M
Jeetendra
Eswaraka
E
Bächi
Thomas
T
Horvath
Edit
E
Hengartner
Hans
H
Whitt
Michael A
MA
de la Torre
Juan Carlos
JC
Zinkernagel
Rolf M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000276:immunology / Q000648:ultrastructure
D000914:Antibodies, Viral; D000954:Antigens, Surface; D000956:Antigens, Viral