A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication afer heterosubtypic influenza a virus challenge

Timothy D. Carroll, Sinthujan Jegaskanda, Shannon R. Matzinger, Linda Fritts, Michael B. McChesney, Stephen J. Kent, Jeffery Fairman, Christopher J. Miller

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background. Influenza A virus (IAV) vaccines ofler 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. Afer 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 signifcantly lower than in unvaccinated control RMs. Heterosubtypic protection in H3-WIV/CLDC RMs was associated with signifcantly higher levels of nucleoprotein (NP) and matrix-1-specifc immunoglobulin G antibodies (P < 0.05) and NP-specifc 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 afer heterosubtypic influenza virus challenge.

Original languageEnglish
Pages (from-to)856-867
Number of pages12
JournalJournal of Infectious Diseases
Volume218
Issue number6
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Cross-reactive
  • NK cell activation
  • Non-neutralizing antibodies

Cite this

Carroll, Timothy D. ; Jegaskanda, Sinthujan ; Matzinger, Shannon R. ; Fritts, Linda ; McChesney, Michael B. ; Kent, Stephen J. ; Fairman, Jeffery ; Miller, Christopher J. / A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication afer heterosubtypic influenza a virus challenge. In: Journal of Infectious Diseases. 2018 ; Vol. 218, No. 6. pp. 856-867.
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title = "A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication afer heterosubtypic influenza a virus challenge",
abstract = "Background. Influenza A virus (IAV) vaccines ofler 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. Afer 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 signifcantly lower than in unvaccinated control RMs. Heterosubtypic protection in H3-WIV/CLDC RMs was associated with signifcantly higher levels of nucleoprotein (NP) and matrix-1-specifc immunoglobulin G antibodies (P < 0.05) and NP-specifc 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 afer heterosubtypic influenza virus challenge.",
keywords = "Cross-reactive, NK cell activation, Non-neutralizing antibodies",
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A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication afer heterosubtypic influenza a virus challenge. / Carroll, Timothy D.; Jegaskanda, Sinthujan; Matzinger, Shannon R.; Fritts, Linda; McChesney, Michael B.; Kent, Stephen J.; Fairman, Jeffery; Miller, Christopher J.

In: Journal of Infectious Diseases, Vol. 218, No. 6, 01.01.2018, p. 856-867.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication afer heterosubtypic influenza a virus challenge

AU - Carroll, Timothy D.

AU - Jegaskanda, Sinthujan

AU - Matzinger, Shannon R.

AU - Fritts, Linda

AU - McChesney, Michael B.

AU - Kent, Stephen J.

AU - Fairman, Jeffery

AU - Miller, Christopher J.

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N2 - Background. Influenza A virus (IAV) vaccines ofler 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. Afer 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 signifcantly lower than in unvaccinated control RMs. Heterosubtypic protection in H3-WIV/CLDC RMs was associated with signifcantly higher levels of nucleoprotein (NP) and matrix-1-specifc immunoglobulin G antibodies (P < 0.05) and NP-specifc 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 afer heterosubtypic influenza virus challenge.

AB - Background. Influenza A virus (IAV) vaccines ofler 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. Afer 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 signifcantly lower than in unvaccinated control RMs. Heterosubtypic protection in H3-WIV/CLDC RMs was associated with signifcantly higher levels of nucleoprotein (NP) and matrix-1-specifc immunoglobulin G antibodies (P < 0.05) and NP-specifc 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 afer heterosubtypic influenza virus challenge.

KW - Cross-reactive

KW - NK cell activation

KW - Non-neutralizing antibodies

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