A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

Int Immunol. 2004 Oct;16(10):1423-30. doi: 10.1093/intimm/dxh143. Epub 2004 Aug 16.

Abstract

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Alum Compounds / administration & dosage
  • Animals
  • Antibody Formation*
  • Antibody Specificity
  • Blotting, Western
  • Immunoglobulin G / blood
  • Injections, Subcutaneous
  • Mice
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Vaccines, Inactivated / administration & dosage
  • Viral Proteins / immunology
  • Viral Vaccines / administration & dosage*
  • Virion / immunology*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Immunoglobulin G
  • Vaccines, Inactivated
  • Viral Proteins
  • Viral Vaccines
  • aluminum sulfate