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J Infect Dis. 2018 Apr 26. doi: 10.1093/infdis/jiy238. [Epub ahead of print]
A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication after heterosubtypic influenza A virus challenge.
Carroll TD1,2, Jegaskanda S3, Matzinger SR1,2, Fritts L1,2, McChesney MB2, Kent SJ3,4,5,6, Fairman J7, Miller CJ1,2,8.
Author information
Abstract
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 influenza A virus vaccine (WIV).
Methods:
Adult rhesus macaques (RM) were vaccinated and at two weeks boosted with either a H1N1-WIV or a H3N2-WIV, with and without CLDC adjuvant. Four weeks post-boost, animals were challenged with a H1N1 influenza A virus matched to the H1N1-WIV vaccine.
Results:
After challenge, vRNA levels in the trachea of control RM and RM vaccinated with the unadjuvanted H1 or H3 WIV vaccines were similar. However, vRNA levels in the trachea of both the H1-WIV/CLDC (p<0.01) and the H3-WIV/CLDC (p<0.05) vaccinated RM were significantly lower than in unvaccinated control RM. Heterosubtypic protection in H3-WIV/CLDC RM was associated with significantly higher levels of nucleoprotein (NP) and matrix-1 (M1)-specific IgG antibodies (p<0.05 or greater) and NP-specific non-neutralizing antibody dependent natural killer (NK) cell activation (p<0.01) compared to unprotected H3-WIV RM.
Conclusions:
Addition of the CLDC adjuvant to a simple WIV elicited immunity to conserved virus structural proteins in RM that correlate with protection from uncontrolled virus replication after heterosubtypic influenza virus challenge.
PMID: 29701840 DOI: 10.1093/infdis/jiy238
A lipid/DNA adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication after heterosubtypic influenza A virus challenge.
Carroll TD1,2, Jegaskanda S3, Matzinger SR1,2, Fritts L1,2, McChesney MB2, Kent SJ3,4,5,6, Fairman J7, Miller CJ1,2,8.
Author information
Abstract
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 influenza A virus vaccine (WIV).
Methods:
Adult rhesus macaques (RM) were vaccinated and at two weeks boosted with either a H1N1-WIV or a H3N2-WIV, with and without CLDC adjuvant. Four weeks post-boost, animals were challenged with a H1N1 influenza A virus matched to the H1N1-WIV vaccine.
Results:
After challenge, vRNA levels in the trachea of control RM and RM vaccinated with the unadjuvanted H1 or H3 WIV vaccines were similar. However, vRNA levels in the trachea of both the H1-WIV/CLDC (p<0.01) and the H3-WIV/CLDC (p<0.05) vaccinated RM were significantly lower than in unvaccinated control RM. Heterosubtypic protection in H3-WIV/CLDC RM was associated with significantly higher levels of nucleoprotein (NP) and matrix-1 (M1)-specific IgG antibodies (p<0.05 or greater) and NP-specific non-neutralizing antibody dependent natural killer (NK) cell activation (p<0.01) compared to unprotected H3-WIV RM.
Conclusions:
Addition of the CLDC adjuvant to a simple WIV elicited immunity to conserved virus structural proteins in RM that correlate with protection from uncontrolled virus replication after heterosubtypic influenza virus challenge.
PMID: 29701840 DOI: 10.1093/infdis/jiy238