Novavax, Inc. reported preclinical study results showing that an investigational H1N1 virus-like particle (VLP) vaccine based on the 1918 Spanish influenza strain protected against both the Spanish flu and a highly pathogenic H5N1 avian influenza strain. The study was conducted by scientists from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA and Novavax under a Collaborative Research and Development Agreement.
Novavax scientists designed and produced a recombinant VLP vaccine candidate against the 1918 H1N1 influenza strain. Mice and ferrets were vaccinated with VLPs by one of two routes: either by standard intramuscular injection, or by administering a small drop of the VLP vaccine in the nose (intranasal immunization). All of the 1918 VLP-immunized animals were protected when exposed to a lethal dose of the 1918 influenza virus, regardless of the route by which the vaccine was administered. Remarkably, animals immunized by the intranasal route were also protected against a lethal dose of a contemporary, highly pathogenic avian influenza subtype H5N1 virus strain, isolated from a fatal human case in 2004 (A/Vietnam/1203/2004 strain).
The H1N1 VLP vaccine candidate was made up of the hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins from 1918 Spanish influenza virus strains. These proteins, which were produced in insect cells, formed three-dimensional structures that mimic the 1918 pandemic influenza virus but without the genetic material needed for replication. The mechanism of action by which this H1N1 VLP vaccine candidate provided broad cross protection is under further study, but the scientists described preliminary evidence that antibody cross-reactivity between the HA and possibly NA proteins of the H1N1 and H5N1 influenza were important.
‘Unlike other non-live influenza vaccines, the VLPs are uniquely positioned to stimulate immunity through multiple mechanisms,’ said Dr. Penny Heaton, Chief Medical Officer at Novavax. ‘First, they contain HA protein that is the same structure as the live virus, which may stimulate HA antibodies of several types that not only prevent the virus from attaching to cells but also prevent the virus from fusing with cells. Second, the VLPs contain NA which may stimulate production of antibody that prevents spread of the virus down the respiratory tract. Finally, the structure of the HA and NA proteins and the way in which they are embedded in lipids on the surface of the VLP may activate the innate immune system providing protection against both the H1N1 and H5N1 strains,’ said Dr. Heaton.
Although cross protection against influenza strains of the same hemagglutinin or HA type has been achieved through the use of vaccines with adjuvants (e.g., cross-protection against H5N1 A/Vietnam and A/Indonesia strains), protection against strains with different HA types, as shown in this study, has not been reported. Cross-protection against different HA types is highly desirable for pandemic influenza vaccine candidates because it is not possible to predict the strain that may be responsible for the next pandemic with today’s technology. A broadly cross protective vaccine would be ideal for stockpiling in that it could be administered during the first wave of the pandemic while waiting for manufacture of vaccine specific to the pandemic strain.
Dr. Gale Smith, Vice President of Vaccine Development at Novavax, said, ‘The discovery that a VLP-based influenza vaccine candidate created through cell-based recombinant technology has the potential to protect against diverse strains of influenza has significant implications for both pre-pandemic and pandemic preparedness. A broadly protective vaccine administered prior to and during the first wave of a pandemic could prevent widespread morbidity and mortality from a newly emerged pandemic influenza strain and allow time for the development of strain-specific vaccines.’
Release Date: April 14, 2009