Biology subjects

Cull, J. W.

Publications and source records attributed to Cull, J. W..

3 recordsLinked to original sources

bioRxiv2025

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.

immunology↗

bioRxiv2024

A Potent Pandemic Avian Influenza Virus Vaccine Based on a 4th Generation Fully Deleted Adenoviral Vector

The GreVac system was developed as a fast and flexible plug- and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors. The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuraminidase influenza genes. Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra muscular (i.m.) delivery route of GreFluVie5 was more efficient than sub cutaneous (s.c.) or intra nasal ones (i.n.). Based on results of this animal trail and GreVacs intrinsic versatility and fast development time, we believe that this platform is ideally suited to swiftly deliver powerful vaccines to infectious diseases with high eruption potentials.

immunology↗

bioRxiv2024

Protecting Allogeneic Pancreatic Islet Grafts by Engineered Veto

In todays clinical practice, general immune suppression regimens are used to prevent transplant rejection. Though highly effective, they impair a patients protection against infectious challenges. Strategies are being sought that prevent graft rejection without inhibiting beneficial immune functions. One such approach is based on the classical veto effect that employs donor-derived CD8+ T cells to inhibit cellular immune responses. Yet, allogeneic grafts may only be partially protected by classical veto as CD8+ T cells may fail to remove organ-specific alloreactive T cells. To induce transplant specific immune unresponsiveness, if not tolerance, it may be necessary to endow grafted tissues with veto. Adenoviral vectors were designed that expressed the CD8 -chain as transgene and thus conferred the immune inhibitory veto function to cells of grafted tissues. In the present model, adenoviral vector vectors protected transduced allogeneic pancreatic islets from rejection in fully immune competent recipients. These studies demonstrated that a tissue-engineering approached could be used to create universally acceptable transplants.

immunology↗