SynCon® influenza vaccines

Influenza virus image

Influenza is one of the most communicable diseases. An influenza season usually strikes both the northern and southern hemispheres each year, resulting in three to five million cases of severe illness and up to 500,000 deaths annually. It is typically most severe in young children and the elderly.

There are many influenza subtypes, the key seasonal subtypes currently of concern to humans being Type A H1N1 and H3N2 as well as Type B influenza. Type A H2N2 and H7N2 have created concern in the recent past. Type A H5N1 is the subtype creating the greatest pandemic concern, i.e. with the ability to affect a wide geographic area and large proportion of the population. Within subtypes there can be hundreds or thousands of strains, often grouped in clades or branches with a degree of similarity. New influenza strains are commonly produced by mutation (“drift”) or less frequently by reassortment (“shift”), which is when two different subtypes infect the cell of an animal or human and blend to create a new subtype.

The protective capability of currently available influenza vaccines is substantially limited. Each year, two Type A strains (currently H1N1 and H3N2) and one Type B strain determined to be of greatest concern in the upcoming influenza season are selected for and manufactured as the vaccine for the upcoming season. Because the vaccine must match the targeted virus strains in order to provide protection, if the selected strain(s) mutates prior to or during the flu season, that season’s vaccine may not provide protection, the most recent example being the 2009 outbreak of H1N1 of swine origin. In addition, older people are not as capable of generating strong antibody immune responses, even with conventional vaccination, and are more susceptible to influenza.

Rather than simply trying to develop and manufacture new influenza vaccines more quickly to counteract the emergence of new virus strains, which is the focus on many influenza R&D programs, the more important need is to create influenza vaccine technology capable of providing truly preemptive long term protection: this is one of Inovio's goals. The ideal would be to achieve a universal influenza vaccine capable of broad protection against existing and newly emergent unmatched strains. In addition, medical scientists believe that generating T-cell responses to fight an established influenza infection may be an effective approach to combating influenza in the elderly. Achieving this capability with new vaccine technology could potentially transform our approach to fighting influenza.

Inovio is approaching this dynamic influenza challenge with a unique strategy to create universal influenza vaccines capable of inducing both preventive antibody and killer T-cell immune responses and providing cross-strain protection against known and new unmatched viruses. Using our synthetic consensus design approach, we have created DNA “constructs” for key virus clades (branches) within the Type A subtypes H1N1, H2N2, H3N2, H7N9, and H5N1 as well as Type B and targeting multiple influenza antigens, including the most frequently changing HA antigen. We can mix and match these individual DNA plasmid constructs as desired to create vaccine candidates. Moreover, our SynCon® vaccines are capable of generating strong T-cell immune responses.

Our clinical development strategy is to assess different combinations of subtypes, constructs, antigens, and electroporation delivery conditions.  We currently have one program comprised of both pandemic and seasonal influenza subtypes for the purpose of assessing a multi-subtype vaccine, however, our strategy is particularly focused on creating a pandemic vaccine targeting H5N1 and a seasonal vaccine encompassing H1N1, H3N2, and Type B (with the ability to add in other subtypes as warranted). We have initiated multiple clinical studies to advance us toward our goal.

                               Influenza sub-types responsible for key flu outbreaks 
         Universal influenza vaccine approach

Program Target Subtypes Target Antigens Trial Subjects Collaborators
 Pandemic  H5N1  HA, NA, NP  Healthy
 Age: 18 - 50
 
 Seasonal  H5N1, H1N1  HA  Healthy
 Age: 18 - 55
 NIH Director's Office Transformative Research Award
 Seasonal  H1N1  HA  Healthy
 Age: 65+
 Public Health Agency of Canada