A Highly Protective Clade 1 and 2 Cross-Reactive Pandemic Influenza Virus Vaccine Based on a 4th Generation Fully Deleted Adenoviral Vector of a Rare Serotype

The GreVac vaccine technology was created as a fast and flexible plug-and-play vaccine platform based on a 4th generation architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors. For the initial proof-of-principle studies, we at Greffex had engineered an avian influenza vaccine, which delivered a transgene expression cassette for an avian influenza virus H5 hemagglutinin and N1 neuraminidase genes in a capsid of the common human Ad serotype 5 (Ad5). This vaccine proved highly immunogenic and protective in mice. These studies revealed that intramuscular ( i.m. ) delivery proved more efficient than subcutaneous ( s.c. ) or intranasal ( i.n. ) routes. In the human population, pre-exposure to the Ad5 virus is common. To minimize interference by pre-existing anti-Ad5 immunities, we created a new GreVac-based avian influenza vaccine, in which the fd Ad genome was packaged into a capsid of the rare human Ad serotype 6 (Ad6). We now report that at very low doses, the resulting GreFluVie6 vaccine given i.m. fully protected mice and ferrets against lethal challenges with the clade 1 A/Vietnam/1203/2004 avian influenza virus associated with induction of potent immune cellular and humoral immune responses. The recipients’ serum antibodies strongly cross-reacted with clade 2.1.3.2 ( A/Indonesia/05/2005 ) and clade 2.3.4.4b H5 hemagglutinins.