Intranasal inoculate of influenza virus vaccine against lethal virus challenge

Vaccine. 2018 Jul 5;36(29):4354-4361. doi: 10.1016/j.vaccine.2018.05.075. Epub 2018 Jun 4.

Abstract

Vaccine adjuvants are essential for enhancing immune responses during vaccination. However, only a limited number of safe and effective adjuvants, especially mucosal adjuvants, are available for use in vaccines. The development of a practically applicable mucosal adjuvant is therefore urgently needed. Here, we showed that the non-toxic CTA1-DD adjuvant, which combined the full enzymatic activity of the A1 subunit of cholera toxin (CT) with two immunoglobulin-binding domains of Staphylococcus aureus protein A (SpA), promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal administration with H1N1 split vaccine in mice. We demonstrated that CTA1-DD-adjuvant vaccine provided 100% protection against mortality and greatly reduced morbidity in a mouse model. We also showed that addition of CTA1-DD to the vaccine elicited significantly higher hemagglutination inhibition titers and IgG antibodies in sera than alum adjuvant. Furthermore, CTA1-DD significantly promoted the production of mucosal secretory IgA in lung lavages and vaginal lavages. We also showed that CTA1-DD could be used as a mucosal adjuvant to enhance T cell responses. Our results clearly indicated that CTA1-DD contributed to the elicitation of a protective cell-mediated immune response required for efficacious vaccination against influenza virus, which suggested that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for respiratory diseases and other mucosal diseases.

Keywords: CTA1-DD; H1N1; Influenza vaccine; Mucosal adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Body Fluids / immunology
  • Bronchoalveolar Lavage
  • Cholera Toxin / administration & dosage*
  • Female
  • Hemagglutination Inhibition Tests
  • Immunoglobulin A, Secretory / analysis
  • Immunoglobulin G / blood
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control*
  • Recombinant Fusion Proteins / administration & dosage*
  • Survival Analysis
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Vaginal Douching

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • CTA1-DD protein, recombinant
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Inactivated
  • Cholera Toxin