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

Abstract

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.