PMID- 15467838
OWN - NLM
STAT- MEDLINE
DCOM- 20041122
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 114
IP  - 7
DP  - 2004 Oct
TI  - Kinetics of protective antibodies are determined by the viral surface antigen.
PG  - 988-93
AB  - 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.
FAU - Pinschewer, Daniel D
AU  - Pinschewer DD
AD  - Institute of Experimental Immunology, Department of Pathology, University 
      Hospital of Zurich, Zurich, Switzerland. pinschi@pathol.unizh.ch
FAU - Perez, Mar
AU  - Perez M
FAU - Jeetendra, Eswaraka
AU  - Jeetendra E
FAU - Bachi, Thomas
AU  - Bachi T
FAU - Horvath, Edit
AU  - Horvath E
FAU - Hengartner, Hans
AU  - Hengartner H
FAU - Whitt, Michael A
AU  - Whitt MA
FAU - de la Torre, Juan Carlos
AU  - de la Torre JC
FAU - Zinkernagel, Rolf M
AU  - Zinkernagel RM
LA  - eng
GR  - R01 AI047140/AI/NIAID NIH HHS/United States
GR  - R56 AI047140/AI/NIAID NIH HHS/United States
GR  - AI-47140/AI/NIAID NIH HHS/United States
GR  - GM-53726/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antigens, Surface)
RN  - 0 (Antigens, Viral)
SB  - IM
CIN - J Clin Invest. 2004 Oct;114(7):895-7. PMID: 15467827
MH  - Animals
MH  - Antibodies, Viral/*immunology
MH  - Antigens, Surface/genetics/*immunology
MH  - Antigens, Viral/genetics/*immunology
MH  - Cell Line
MH  - Lymphocytic choriomeningitis virus/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Vesicular stomatitis Indiana virus/genetics/metabolism
MH  - Virion/immunology/ultrastructure
PMC - PMC518669
EDAT- 2004/10/07 09:00
MHDA- 2004/12/16 09:00
PMCR- 2004/10/01
CRDT- 2004/10/07 09:00
PHST- 2004/06/08 00:00 [received]
PHST- 2004/07/27 00:00 [accepted]
PHST- 2004/10/07 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/07 09:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 22374 [pii]
AID - 10.1172/JCI22374 [doi]
PST - ppublish
SO  - J Clin Invest. 2004 Oct;114(7):988-93. doi: 10.1172/JCI22374.