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Vaccine
Article in Press, Uncorrected Proof - Note to users
doi:10.1016/j.vaccine.2011.07.099 | How to Cite or Link Using DOI
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Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico
Constantino L?pez-Mac?asa, Corresponding Author Contact Information, E-mail The Corresponding Author, Eduardo Ferat-Osorioa, Alejandra Tenorio-Calvola, c, Armando Isibasia, Juan Talaverab, Oscar Arteaga-Ruiza, Lourdes Arriaga-Pizanoa, Somia P. Hickmane, Mar?a Allended, Kathy Lenharde, Steven Pincuse, Kevin Connollyf, Ramadevi Raghunandane, Gale Smithe and Gregory Glenne, Corresponding Author Contact Information, E-mail The Corresponding Author, E-mail The Corresponding Author
a Medical Research Unit on Immunochemistry, Specialities Hospital of the National Medical Centre ?Siglo XXI? Mexican Social Security Institute (IMSS), Mexico City, Mexico
b Epidemiology Research Unit, Specialities Hospital of the National Medical Centre ?Siglo XXI? IMSS, Mexico City, Mexico
c Biomedicine and Molecular Biotechnology Program, Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico
d 503 Baltimore Road, Rockville, MD, USA
e Novavax, Inc., 9920 Belward Campus Drive, Rockville, MD 20850, USA
f Pharmathene, One Park Place, Suite 450, Annapolis, MD, USA
Received 11 May 2011;
revised 12 July 2011;
accepted 20 July 2011.
Available online 2 August 2011.
Abstract
Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18?64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 μg, 15 μg, or 45 μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 μg VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 μg and 45 μg) compared to the placebo and 5 μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82?92% of all subjects and in 64?85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.
Highlights
► The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted during the H1N1 2009 pandemic in Mexico. ► The H1N1 2009 VLP vaccine was safe and well-tolerated with no vaccine-related serious adverse events. ► The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, which were statistically higher compared to placebo.
http://www.sciencedirect.com/science/article/pii/S0264410X11011492
Article in Press, Uncorrected Proof - Note to users
doi:10.1016/j.vaccine.2011.07.099 | How to Cite or Link Using DOI
Permissions & Reprints
Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico
Constantino L?pez-Mac?asa, Corresponding Author Contact Information, E-mail The Corresponding Author, Eduardo Ferat-Osorioa, Alejandra Tenorio-Calvola, c, Armando Isibasia, Juan Talaverab, Oscar Arteaga-Ruiza, Lourdes Arriaga-Pizanoa, Somia P. Hickmane, Mar?a Allended, Kathy Lenharde, Steven Pincuse, Kevin Connollyf, Ramadevi Raghunandane, Gale Smithe and Gregory Glenne, Corresponding Author Contact Information, E-mail The Corresponding Author, E-mail The Corresponding Author
a Medical Research Unit on Immunochemistry, Specialities Hospital of the National Medical Centre ?Siglo XXI? Mexican Social Security Institute (IMSS), Mexico City, Mexico
b Epidemiology Research Unit, Specialities Hospital of the National Medical Centre ?Siglo XXI? IMSS, Mexico City, Mexico
c Biomedicine and Molecular Biotechnology Program, Biochemistry Department, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico
d 503 Baltimore Road, Rockville, MD, USA
e Novavax, Inc., 9920 Belward Campus Drive, Rockville, MD 20850, USA
f Pharmathene, One Park Place, Suite 450, Annapolis, MD, USA
Received 11 May 2011;
revised 12 July 2011;
accepted 20 July 2011.
Available online 2 August 2011.
Abstract
Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18?64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 μg, 15 μg, or 45 μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 μg VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 μg and 45 μg) compared to the placebo and 5 μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82?92% of all subjects and in 64?85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.
Highlights
► The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted during the H1N1 2009 pandemic in Mexico. ► The H1N1 2009 VLP vaccine was safe and well-tolerated with no vaccine-related serious adverse events. ► The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, which were statistically higher compared to placebo.
http://www.sciencedirect.com/science/article/pii/S0264410X11011492