Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo, ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13–877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.
DelmasB.,
GelfiJ.,
LaudeH.1986; Antigenic structure of transmissible gastroenteritis virus. II. Domains in the peplomer glycoprotein. J Gen Virol 67:1405–1418[CrossRef]
DrostenC.,
GuntherS.,
PreiserW.23 other authors2003; Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348:1967–1976[CrossRef]
GuanY.,
ZhengB. J.,
HeY. Q.15 other authors2003; Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302:276–278[CrossRef]
LiW.,
MooreM. J.,
VasilievaN.9 other authors2003; Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454[CrossRef]
NasonE. L.,
WetzelJ. D.,
MukherjeeS. K.,
BartonE. S.,
PrasadB. V.,
DermodyT. S.2001; A monoclonal antibody specific for reovirus outer-capsid protein σ 3 inhibits σ 1-mediated hemagglutination by steric hindrance. J Virol 75:6625–6634[CrossRef]
OberlinE.,
AmaraA.,
BachelerieF.10 other authors1996; The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382:833–835[CrossRef]
PoutanenS. M.,
LowD. E.,
HenryB.11 other authors2003; Identification of severe acute respiratory syndrome in Canada. N Engl J Med 348:1995–2005[CrossRef]
RiscoC.,
AntonI. M.,
SuneC.,
PedregosaA. M.,
Martin-AlonsoJ. M.,
ParraF.,
CarrascosaJ. L.,
EnjuanesL.1995; Membrane protein molecules of transmissible gastroenteritis coronavirus also expose the carboxy-terminal region on the external surface of the virion. J Virol 69:5269–5277
RotaP. A.,
ObersteM. S.,
MonroeS. S.32 other authors2003; Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394–1399[CrossRef]
TrkolaA.,
DragicT.,
ArthosJ.7 other authors1996; CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384:184–187[CrossRef]
VennemaH.,
de GrootR. J.,
HarbourD. A.,
DalderupM.,
Gruffydd-JonesT.,
HorzinekM. C.,
SpaanW. J.1990; Early death after feline infectious peritonitis virus challenge due to recombinant vaccinia virus immunization. J Virol 64:1407–1409
WongS. K.,
LiW.,
MooreM. J.,
ChoeH.,
FarzanM.2003; A 193-amino-acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem 279:3197–3201[CrossRef]
WoodsR. D.,
WesleyR.,
KapkeP. A.1987; Complement-dependent neutralization of transmissible gastroenteritis virus by monoclonal antibodies. Adv Exp Med Biol 218:493–500
WuL.,
GerardN. P.,
WyattR.9 other authors1996; CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor. Nature 384:179–183[CrossRef]
YountB.,
CurtisK. M.,
FritzE. A.,
HensleyL. E.,
JahrlingP. B.,
PrenticeE.,
DenisonM. R.,
GeisbertT. W.,
BaricR. S.2003; Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 100:12995–13000[CrossRef]
Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine