Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization.
Although the initial isolates of the severe acute respiratory syndrome (SARS) coronavirus (CoV) are sensitive to neutralization by antibodies through their spike (S) glycoprotein, variants of S have since been identified that are resistant to such inhibition. Optimal vaccine strategies would therefore make use of additional determinants of immune recognition, either through cellular or expanded, cross-reactive humoral immunity. Here, the cellular and humoral immune responses elicited by different combinations of gene-based and inactivated viral particles with various adjuvants have been assessed. The T-cell response was altered by different prime-boost immunizations, with the optimal CD8 immunity induced by DNA priming and replication-defective adenoviral vector boosting. The humoral immune response was enhanced most effectively through the use of inactivated virus with adjuvants, either MF59 or alum, and was associated with stimulation of the CD4 but not the CD8 response. The use of inactivated SARS virus with MF59 enhanced the CD4 and antibody response even after gene-based vaccination. Because both cellular and humoral immune responses are generated by gene-based vaccination and inactivated viral boosting, this strategy may prove useful in the generation of SARS-CoV vaccines.
Kong
Wing-pui
WP
Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA.
Xu
Ling
L
Stadler
Konrad
K
Ulmer
Jeffrey B
JB
Abrignani
Sergio
S
Rappuoli
Rino
R
Nabel
Gary J
GJ
D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV