Immunogenicity of H5N1 Vaccine Following H5N2

• ClinicalTrials.gov Identifier: NCT02153671
• Recruitment Status: Completed
• First Posted: June 3, 2014
• Results First Posted: February 18, 2019
• Last Update Posted: February 18, 2019
• Sponsor: PATH
• Collaborators: Institute of Experimental Medicine, Russia; Research Institute of Influenza, Russia
• Information provided by (Responsible Party): PATH

Tracking Information

• First Submitted Date: May 23, 2014
• First Posted Date: June 3, 2014
• Results First Submitted Date: August 7, 2018
• Results First Posted Date: February 18, 2019
• Last Update Posted Date: February 18, 2019
• Study Start Date: May 2014
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 14, 2019)

• Geometric Mean Titer of Serum Hemagglutination Inhibition Antibody Response to A/17/Duck/Potsdam/86/92 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional World Health Organization (WHO)-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells. A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Geometric Mean Titer of Serum Hemagglutination Inhibition Antibody Response to A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells. A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Geometric Mean Titer of Serum Hemagglutination Inhibition Antibody Response to A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells. A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Geometric Mean Titer of Serum Hemagglutination Inhibition Antibody Response to A/Turkey/Turkey/5/05(H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells. A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Geometric Mean Titer of Microneutralization Antibody Response to A/17/Turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50).
• Geometric Mean Titer of Microneutralization Antibody Response to A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50).
• Number and Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Antibody Against 17/t/Tur (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Antibody Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Antibody Against A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Antibody Against A/17/Duck/Potsdam/86/92 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroconversion for Microneutralization (MN) Antibody Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50). A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Number and Percentage of Subjects With Seroconversion for Microneutralization (MN) Antibody Against A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50). A four-fold or greater antibody rise in titer was considered to be a seroconversion.
• Number and Percentage of Subjects With Seroprotective Titers for Serum Hemagglutination Inhibition (HAI) Antibody Against 17/t/Tur (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Seroprotection was defined as ≥1:40 antibody titer. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroprotective Titer of Serum Hemagglutination Inhibition (HAI) Antibody Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Seroprotection was defined as ≥1:40 antibody titer. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroprotective Titer of Serum Hemagglutination Inhibition (HAI) Antibody Against A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Seroprotection was defined as ≥1:40 antibody titer. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroprotective Titer of Serum Hemagglutination Inhibition (HAI) Antibody Against A/17/Duck/Potsdam/86/92 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Seroprotection was defined as ≥1:40 antibody titer. The following H5 antigens were tested to evaluate the breadth of the response: i) A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)); ii) A/turkey/Turkey/5/05(H5N1) PR8-based candidate vaccine virus (NIBRG-23 (H5N1)); iii) A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1)); and iv) A/17/duck/Potsdam/86/92 (H5N2) (d/Pot (H5N2)). HAI tests were performed on serum samples with the conventional WHO-recommended assays. Sera were pretreated with receptor destroying enzyme (RDE, Denka Seiken, Japan) and tested against 4 HA units of several H5 antigens using horse red blood cells.
• Number and Percentage of Subjects With Seroprotective Titer of Microneutralization (MN) Antibody Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50). Seroprotection was defined as ≥1:40 antibody titer.
• Number and Percentage of Subjects With Seroprotective Titer of Microneutralization (MN) Antibody Against A/Indonesia/5/2005 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Serum specimens were tested for neutralizing antibodies against A/17/turkey/Turkey/05/133 (H5N2) (17/t/Tur (H5N2)) LAIV strain and A/Indonesia/5/2005 (H5N1) PR8-based candidate vaccine virus (Indo (H5N1) by MN using Madin-Darby Canine Kidney cells. Titers of neutralizing antibodies were expressed as reciprocal of the greatest dilution giving a neutralization of 50% on the cytopathic effects of the virus in the tissue culture (TCID50). Seroprotection was defined as ≥1:40 antibody titer.
• Geometric Mean Titer of Serum Immunoglobulin A (IgA) Response to A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Geometric Mean Titer of Serum Immunoglobulin A (IgA) Response to A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Geometric Mean Titer of Serum Immunoglobulin G (IgG) Response to A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Geometric Mean Titer of Serum Immunoglobulin G (IgG) Response to A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Number and Percentage of Subjects With Seroconversion for Immunoglobulin A (IgA) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Number and Percentage of Subjects With Seroconversion for Immunoglobulin A (IgA) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Number and Percentage of Subjects With Seroconversion for Immunoglobulin G (IgG) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.
• Number and Percentage of Subjects With Seroconversion for Immunoglobulin G (IgG) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus Following Administration of A(H5N1) Inactivated Influenza Vaccine (IIV) [ Time Frame: 56 days ]
  A four-fold or greater antibody rise in titer was considered to be a seroconversion. Detection of anti-hemagglutinin (HA) immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies was carried out by indirect enzyme-linked immunosorbent assay (ELISA). 16 HA units of sucrose-purified virus antigen was used to coat ELISA plates in a volume of 100 ml. Two-fold dilutions of sera were prepared starting from 1:10 (for IgA antibody) and 1:100 (for IgG antibody) and added to the coated wells, followed by incubation with the horseradish peroxidase-conjugated goat anti-human IgA or IgG.

Original Primary Outcome Measures (submitted: May 30, 2014)

• immunologic response [ Time Frame: 4 weeks following vaccination ]
  Proportion of subjects exhibiting seroresponses in selected assays (HAI, microneutralization and ELISA) in the prime-boost and the control groups. ]
• immunologic response [ Time Frame: 4 weeks after vaccination ]
  Antibody GMTs in each group of study subjects for assays employed.

• Change History: Complete list of historical versions of study NCT02153671 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 14, 2019)

• Number and Percentage of Subjects With ≥15% Increase of Avidity Index in Serum Immunoglobulin A (IgA) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Number and Percentage of Subjects With ≥15% Increase of Avidity Index in Serum Immunoglobulin G (IgG) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Number and Percentage of Subjects With ≥15% Increase of Avidity Index in Serum Immunoglobulin A (IgA) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Number and Percentage of Subjects With ≥15% Increase of Avidity Index in Serum Immunoglobulin G (IgG) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Mean Avidity Index for Serum Immunoglobulin A (IgA) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Mean Avidity Index for Serum Immunoglobulin G (IgG) Against A/17/Turkey/Turkey/05/133 (H5N2) LAIV Strain After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Mean Avidity Index for Serum Immunoglobulin A (IgA) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.
• Mean Avidity Index for Serum Immunoglobulin G (IgG) Against A/Turkey/Turkey/5/05 (H5N1) PR8-based Candidate Vaccine Virus After Receiving One Dose of A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 28 days ]
  The avidity index (AI) was defined as the ratio of the mean optical density at 450 nm (OD450) with urea to that without urea, multiplied by 100. A 15% increase in the AI value was considered significant.

Original Secondary Outcome Measures (submitted: May 30, 2014)

safety [ Time Frame: 4 weeks after each vaccination ]

Post-vaccination local and systemic reactogenicity and adverse events to the OrniFlu® inactivated influenza vaccine in subjects previously primed with LAIV H5N2 and in naïve subjects.

Current Other Pre-specified Outcome Measures (submitted: February 14, 2019)

• Number of Subjects Experiencing Adverse Events After Receiving A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 56 days ]
  Subjects were asked to closely watch for and report any adverse events occurring the first 6 days after immunization, and followed for any reactions and adverse events occurring within 7 and 28 days after each vaccination.
• Number of Subjects Experiencing Any Adverse Event Related to the A(H5N1) Inactivated Influenza Vaccine [ Time Frame: 56 days ]
  Subjects were asked to closely watch for and report any adverse events occurring the first 6 days after immunization, and followed for any reactions and adverse events occurring within 7 and 28 days after each vaccination

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immunogenicity of H5N1 Vaccine Following H5N2
• Official Title: Immunogenicity of OrniFlu® Inactivated Influenza Vaccine in Subjects Previously Immunized With Live Attenuated H5N2 Influenza Vaccine and in Non-vaccinated Subjects
• Brief Summary: This study is designed to assess whether a live attenuated Influenza vaccine (LAIV) can induce a long-lasting immune memory by comparing the immunologic response to two doses of the OrniFlu® inactivated vaccine given to subjects previously primed with LAIV and subjects who did not received LAIV.
• Detailed Description: This study evaluated immunogenicity of an adjuvanted A(H5N1) inactivated influenza vaccine (IIV) in healthy adult subjects who received A(H5N2) live attenuated influenza vaccine (LAIV) 1.5 years earlier (September/October 2012) and compared this with a group of naive subjects that did not participate in the previous study. Inclusion/exclusion criteria for the additional group of naive volunteers mirrored those utilized in the initial study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Influenza Vaccine

Intervention

• Biological: A(H5N1) inactivated influenza vaccine (IIV)
  Prepared from the NIBRG-23 vaccine virus strain. One vaccine dose (0.5 ml) contained 15 mg of influenza A(H5N1) virus hemagglutinin (HA), adjuvanted with aluminum hydroxide. Two doses were administered intramuscularly 28 days apart.
  Other Name: Orniflu
• Biological: A(H5N2) live attenuated influenza vaccine (LAIV)
  Two doses of A(H5N2) live attenuated influenza vaccine (LAIV) administered 28 days apart, approximately 1.5 years prior to receiving A(H5N1) IIV

Study Arms

• Experimental: Primed with H5N2
  Subjects who received A(H5N1) inactivated influenza vaccine as well as primed with H5N2 live attenuated influenza vaccine approximately 1.5 years before
  Interventions:

  • Biological: A(H5N1) inactivated influenza vaccine (IIV)
  • Biological: A(H5N2) live attenuated influenza vaccine (LAIV)
• Active Comparator: Did not receive A(H5N2)
  Subjects who received A(H5N1) inactivated influenza vaccine and did not receive A(H5N2) live attenuated influenza vaccine in a previous study.
  Intervention: Biological: A(H5N1) inactivated influenza vaccine (IIV)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 30, 2014): 43
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2014
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Legal male or female adult 18 through 51 years of age at the enrollment visit
• Literate and willing to provide written informed consent
• A signed informed consent
• Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination
• Capable and willing to complete a memory aid and willing to return for all follow-up visits
• For females, willing to take reliable birth control measures through Day 56

Exclusion Criteria:

• Participation in another clinical trial involving any investigational agent within the previous three months or planned enrollment in such a trial during the period of this study
• Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt
• Participation in any other clinical trials involving any H5-matched influenza vaccines except that in Protocol LAIV-H5N2-01
• Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever
• Other acute illness at the time of study enrollment
• Receipt of immunoglobulin or other blood products within three months prior to study enrollment or planned receipt during study period
• Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants and/or immune-modulating therapy within six months prior to study enrollment
• History of bronchial asthma
• Hypersensitivity after previous administration of any (not only influenza) vaccines.
• Other adverse event (AE) following immunization at least possibly related to previous receipt of any (not only influenza) vaccine
• Suspected or known hypersensitivity to any of the study vaccine components, including protein of chicken eggs
• Seasonal (autumnal) hypersensitivity to the natural environment
• Acute or chronic clinically significant abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale will be excluded from entry into the study
• History of leukemia or any other blood diseases or solid organ cancer
• History of thrombocytopenic purpura or known bleeding disorder
• History of seizures
• Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection
• Known chronic hepatitis B virus (HBV) or hepatitis C (HCV) infection
• Known tuberculosis infection or evidence of previous tuberculosis exposure
• History of chronic alcohol abuse and/or illegal drug use

• Pregnancy or lactation.

  • Systemic connective tissue disorders
• Adrenal gland diseases
• Hereditary, degenerative and progredient diseases of the nervous system
• Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives
• Allergic, including anaphylactic, reactions to any (not only influenza) vaccines

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 51 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT02153671
• Other Study ID Numbers: LAIV-H5N2-02
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: PATH
• Study Sponsor: PATH

Collaborators

• Institute of Experimental Medicine, Russia
• Research Institute of Influenza, Russia

Investigators

• Principal Investigator: Oleg I Kiselev, Ph.D.; Research Institute of Influenza

• PRS Account: PATH
• Verification Date: February 2019