A Lipid/DNA Adjuvant-Inactivated Influenza Virus Vaccine Protects Rhesus Macaques From Uncontrolled Virus Replication After Heterosubtypic Influenza A Virus Challenge

J Infect Dis. 2018 Aug 14;218(6):856-867. doi: 10.1093/infdis/jiy238.


Background: Influenza A virus (IAV) vaccines offer little protection from mismatched viruses with antigenically distant hemagglutinin (HA) glycoproteins. We sought to determine if a cationic lipid/DNA complex (CLDC) adjuvant could induce heterosubtypic protection if added to a whole inactivated IAV vaccine (WIV).

Methods: Adult rhesus macaques (RMs) were vaccinated and at 2 weeks boosted with either an H1N1-WIV or an H3N2-WIV, with and without CLDC adjuvant. Four weeks postboost, animals were challenged with an H1N1 IAV matched to the H1N1-WIV vaccine.

Results: After challenge, viral RNA (vRNA) levels in the trachea of control RMs and RMs vaccinated with the unadjuvanted H1 or H3 WIV vaccines were similar. However, vRNA levels in the trachea of both the H1-WIV/CLDC- and the H3-WIV/CLDC-vaccinated RMs (P < 0.01 and P < 0.05, respectively) were significantly lower than in unvaccinated control RMs. Heterosubtypic protection in H3-WIV/CLDC RMs was associated with significantly higher levels of nucleoprotein (NP) and matrix-1-specific immunoglobulin G antibodies (P < 0.05) and NP-specific nonneutralizing antibody-dependent natural killer cell activation (P < 0.01) compared with unprotected H3-WIV RMs.

Conclusions: Addition of the CLDC adjuvant to a simple WIV elicited immunity to conserved virus structural proteins in RMs that correlate with protection from uncontrolled virus replication after heterosubtypic influenza virus challenge.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • DNA / administration & dosage*
  • Disease Models, Animal
  • Female
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / pharmacology
  • Lipids / administration & dosage*
  • Liposomes / administration & dosage
  • Macaca mulatta / immunology
  • Macaca mulatta / virology
  • Male
  • Nucleocapsid Proteins
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Plasmids / genetics
  • RNA-Binding Proteins / immunology
  • Trachea / virology
  • Vaccines, Attenuated / administration & dosage*
  • Vaccines, Attenuated / pharmacology
  • Viral Core Proteins / immunology
  • Virus Replication / drug effects


  • Adjuvants, Immunologic
  • Influenza Vaccines
  • Lipids
  • Liposomes
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Vaccines, Attenuated
  • Viral Core Proteins
  • DNA