Biology subjects

Hartwig, A. T.

Publications and source records attributed to Hartwig, A. T..

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↗

bioRxiv2025

Development of an Intranasally- and Intramuscularly-Administrable Replicon Vaccine Efficacious Against H5N1 Influenza Virus

The risk of a respiratory viral pandemic is significant, including from the now widespread panzootic H5N1 influenza virus, highlighting the need for effective, stable, and inexpensive vaccine technologies that elicit strongly protective immunity. Intranasal vaccines can stimulate local immune responses at the site of natural respiratory viral infection, a key characteristic that can not only reduce morbidity and mortality caused by respiratory viruses but also potentially reduce viral transmissibility to limit outbreaks. Nucleic acid vaccines are now a valuable tool in pandemic responses, with high potency and rapid adaptability to target circulating or emerging viral strains; however, data are limited on which vaccine attributes are needed for efficient transmucosal delivery and immune stimulation following intranasal delivery. To demonstrate proof of concept, here we have developed a replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carrier (NLC) delivery system. A relationship was established between the molar ratio of positive charges on the NLC to the negative charges on the nucleic acid (N:P ratio) and the immunogenicity of the vaccine formulations, with higher N:P ratios resulting in an increase in vaccine immunogenicity. We demonstrated the ability of this replicon vaccine to be administered via intramuscular and intranasal routes with a singular vaccine formulation. The vaccine induced systemic immunity when dosed intramuscularly or intranasally in an immunocompetent mouse model, whereas intranasal dosing uniquely stimulated a strong mucosal immune response. Moreover, a mixed intramuscular/intranasal dosing strategy using this unified formulation stimulated a balanced systemic and mucosal immune response. Finally, we demonstrated the protective efficacy of this intranasally and intramuscularly/intranasally delivered H5 replicon-NLC vaccine against morbidity and mortality in a lethal H5N1 influenza challenge ferret model. This work establishes the replicon-NLC vaccine platform as a potential novel intranasal technology for rapid pandemic response.

immunology↗

bioRxiv2025

An intranasal, NLC-delivered self-amplifying RNA vaccine establishes protective immunity against pre-pandemic H5N1 and H7N9 influenza

Seasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The saRNA-NLC vaccines provided complete protection against morbidity and mortality in ferret challenge models, establishing this intranasally-administered saRNA-NLC vaccine platform as a potential pandemic response tool. ONE SENTENCE SUMMARYA self-amplifying RNA-NLC vaccine, delivered intranasally, induces robust mucosal immunity in mice and protects against H5N1 and H7N9 in ferrets

immunology↗