Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity.

Abstract

We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.

• Authors: Ursula J Buchholz, Alexander Bukreyev, Lijuan Yang, Elaine W Lamirande, Brian R Murphy, Kanta Subbarao, Peter L Collins
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 26 Pg. 9804-9 (Jun 29 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15210961 (Publication Type: Journal Article)

Chemical References

• Antibodies, Viral
• DNA, Recombinant
• Membrane Glycoproteins
• Spike Glycoprotein, Coronavirus
• Viral Envelope Proteins
• Viral Matrix Proteins
• Viral Vaccines
• spike glycoprotein, SARS-CoV

Topics

• Administration, Intranasal
• Animals
• Antibodies, Viral (immunology)
• Cell Line
• Chlorocebus aethiops
• Cricetinae
• DNA, Recombinant (genetics)
• Genetic Vectors (genetics)
• Membrane Glycoproteins (genetics, immunology)
• Neutralization Tests
• Parainfluenza Virus 3, Human (genetics)
• Respiratory System (immunology, virology)
• Severe acute respiratory syndrome-related coronavirus (chemistry, genetics, growth & development, immunology)
• Severe Acute Respiratory Syndrome (immunology, prevention & control, virology)
• Spike Glycoprotein, Coronavirus
• Vaccination
• Vero Cells
• Viral Envelope Proteins (genetics, immunology)
• Viral Matrix Proteins (genetics, immunology)
• Viral Vaccines (administration & dosage, genetics, immunology)
• Virus Replication (physiology)