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Vaccine
Volume 30, Issue 37, 10 August 2012, Pages 5557?5563
Cover image
Efficacy of an AS03A-adjuvanted split H5N1 influenza vaccine against an antigenically distinct low pathogenic H5N1 virus in pigs
Annebel R. De Vleeschauwera, 1,
Beno?t Barasb,
Constantinos S. Kyriakisa, 2,
Val?rie Jacobb,
Camille Plantyb,
Sandra L. Gianninib,
Sally Mossmanb,
Kristien Van Reetha, Corresponding author contact information, E-mail the corresponding author
a Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium
b Preclinical Virology, GlaxoSmithKline Biologicals, rue de l?Institut 89, B-1330 Rixensart, Belgium
Received 11 January 2012. Revised 27 May 2012. Accepted 10 June 2012. Available online 21 June 2012.
Abstract
We used the pig model of influenza to examine the efficacy of an AS03A-adjuvanted split H5N1 (A/Indonesia/05/2005) vaccine against challenge with a low pathogenic (LP) H5N1 avian influenza (AI) virus (duck/Minnesota/1525/1981) with only 85% amino acid homology in its HA1. Influenza seronegative pigs were vaccinated twice intramuscularly with adjuvanted vaccine at 3 antigen doses, unadjuvanted vaccine or placebo. All pigs were challenged 4 weeks after the second vaccination and euthanized 2 days later. After 2 vaccinations, all pigs in the adjuvanted vaccine groups had high hemagglutination inhibiting (HI) antibody titers to the vaccine strain (160?640), and lower antibody titers to the A/Vietnam/1194/04 H5N1 strain and to 2 LP H5 viruses with 90?91% amino acid homology to the vaccine strain (20?160). Eight out of 12 pigs had HI titers (10?20) to the challenge virus immediately before challenge. Neuraminidase inhibiting antibodies to the challenge virus were detected in most pigs (7/12) and virus neutralizing antibodies in all pigs. There was no antigen-dose dependent effect on the antibody response among the pigs immunized with adjuvanted H5N1 vaccines. After challenge, these pigs showed a complete clinical protection, reduced lung lesions and a significant protection against virus replication in the respiratory tract. Though the challenge virus showed only moderate replication efficiency in pigs, our study suggests that AS03A-adjuvanted H5N1 vaccine may confer a broader protection than generally assumed. The pros and cons of the pig as an H5N1 challenge model are also discussed.
Highlights
► Vaccine and challenge H5N1 strains showed only 85% aa homology in their HA1. ► Adjuvanted vaccine induced VN antibodies against the challenge virus in all pigs. ► Adjuvanted vaccine offered a robust virological protection against challenge. ► AS03A-adjuvanted H5N1 vaccine may offer a broader protection than generally assumed. ► The pig model of H5N1 influenza virus challenge can still be improved.
Volume 30, Issue 37, 10 August 2012, Pages 5557?5563
Cover image
Efficacy of an AS03A-adjuvanted split H5N1 influenza vaccine against an antigenically distinct low pathogenic H5N1 virus in pigs
Annebel R. De Vleeschauwera, 1,
Beno?t Barasb,
Constantinos S. Kyriakisa, 2,
Val?rie Jacobb,
Camille Plantyb,
Sandra L. Gianninib,
Sally Mossmanb,
Kristien Van Reetha, Corresponding author contact information, E-mail the corresponding author
a Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium
b Preclinical Virology, GlaxoSmithKline Biologicals, rue de l?Institut 89, B-1330 Rixensart, Belgium
Received 11 January 2012. Revised 27 May 2012. Accepted 10 June 2012. Available online 21 June 2012.
Abstract
We used the pig model of influenza to examine the efficacy of an AS03A-adjuvanted split H5N1 (A/Indonesia/05/2005) vaccine against challenge with a low pathogenic (LP) H5N1 avian influenza (AI) virus (duck/Minnesota/1525/1981) with only 85% amino acid homology in its HA1. Influenza seronegative pigs were vaccinated twice intramuscularly with adjuvanted vaccine at 3 antigen doses, unadjuvanted vaccine or placebo. All pigs were challenged 4 weeks after the second vaccination and euthanized 2 days later. After 2 vaccinations, all pigs in the adjuvanted vaccine groups had high hemagglutination inhibiting (HI) antibody titers to the vaccine strain (160?640), and lower antibody titers to the A/Vietnam/1194/04 H5N1 strain and to 2 LP H5 viruses with 90?91% amino acid homology to the vaccine strain (20?160). Eight out of 12 pigs had HI titers (10?20) to the challenge virus immediately before challenge. Neuraminidase inhibiting antibodies to the challenge virus were detected in most pigs (7/12) and virus neutralizing antibodies in all pigs. There was no antigen-dose dependent effect on the antibody response among the pigs immunized with adjuvanted H5N1 vaccines. After challenge, these pigs showed a complete clinical protection, reduced lung lesions and a significant protection against virus replication in the respiratory tract. Though the challenge virus showed only moderate replication efficiency in pigs, our study suggests that AS03A-adjuvanted H5N1 vaccine may confer a broader protection than generally assumed. The pros and cons of the pig as an H5N1 challenge model are also discussed.
Highlights
► Vaccine and challenge H5N1 strains showed only 85% aa homology in their HA1. ► Adjuvanted vaccine induced VN antibodies against the challenge virus in all pigs. ► Adjuvanted vaccine offered a robust virological protection against challenge. ► AS03A-adjuvanted H5N1 vaccine may offer a broader protection than generally assumed. ► The pig model of H5N1 influenza virus challenge can still be improved.
