Contributions of the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus to Protective Immunity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 26; pp. 9804 - 9809
• Main Authors: Buchholz, Ursula J., Bukreyev, Alexander, Yang, Lijuan, Lamirande, Elaine W., Murphy, Brian R., Subbarao, Kanta, Collins, Peter L., Chanock, Robert M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29.06.2004; National Acad Sciences
• Subjects: Administration, Intranasal; Animals; Antibodies; Antibodies, Viral - immunology; Antigens; Biological Sciences; Cell Line; Chlorocebus aethiops; Coronavirus; Cricetinae; DNA, Recombinant - genetics; Genetic vectors; Genetic Vectors - genetics; Immune response; Immunization; Immunology; Infections; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Microbiology; Neutralization Tests; Open reading frames; Parainfluenza Virus 3, Human - genetics; Respiratory System - immunology; Respiratory System - virology; SARS virus; Severe acute respiratory syndrome; Severe Acute Respiratory Syndrome - immunology; Severe Acute Respiratory Syndrome - prevention & control; Severe Acute Respiratory Syndrome - virology; Severe acute respiratory syndrome-related coronavirus - chemistry; Severe acute respiratory syndrome-related coronavirus - genetics; Severe acute respiratory syndrome-related coronavirus - growth & development; Severe acute respiratory syndrome-related coronavirus - immunology; Spike Glycoprotein, Coronavirus; Vaccination; Vero Cells; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Matrix Proteins - genetics; Viral Matrix Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Replication - physiology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0403492101

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.