Vivaldi Biosciences Inc., a clinical-stage biotechnology company, has signed a Cooperative Research and Development Agreement (CRADA) with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to generate and evaluate in preclinical studies LAIV candidates against influenza A(H7N9). The H7N9 strain is of concern due to its pandemic potential. Human cases of this avian-origin influenza strain were first recognized in early 2013.

“We are pleased that NIAID has taken an active interest in Vivaldi’s NS1-based LAIV platform and reverse genetics technologies by collaborating with the company on this important program for pandemic preparedness. We look forward to working with Dr. Kanta Subbarao and her team at NIAID’s Laboratory of Infectious Diseases”

Vivaldi’s LAIV technology platform uses the biology of the influenza nonstructural protein 1 (NS1) to provide a new vaccine approach with the potential for superior efficacy and protection. NS1 is a multifunctional virulence factor of the influenza virus. Vivaldi uses proprietary reverse genetics and plasmid rescue technologies to modify the NS1 gene, generating replication-deficient LAIVs attenuated for safety and able to produce a potent, protective immune response.

Research under the CRADA will use Vivaldi’s LAIV master strain, which incorporates a specifically truncated NS1 gene and other attenuating genes. The Vivaldi and NIAID teams jointly will select, clone and manipulate H7N9 genes for insertion into Vivaldi’s master strain to generate candidate LAIVs against influenza H7N9. Vivaldi and NIAID together will conduct in vitro and in vivo evaluations of the candidate LAIVs, including studies of safety, immunogenicity and protective efficacy in animal models, and will carry out Good Laboratory Practices (GLP) toxicology evaluations of the candidate LAIVs. Data generated in the programme are expected to support the filing of an Investigational New Drug (IND) application for a phase 1 clinical trial in volunteers.

“We are pleased that NIAID has taken an active interest in Vivaldi’s NS1-based LAIV platform and reverse genetics technologies by collaborating with the company on this important program for pandemic preparedness. We look forward to working with Dr. Kanta Subbarao and her team at NIAID’s Laboratory of Infectious Diseases,” said Douglass B. Given, MD, PhD, President and CEO of Vivaldi. “Promising activity and a favorable safety profile have been demonstrated in a Phase 1 study of our NS1-based LAIV for H5N1 influenza, another strain with pandemic potential. This CRADA with NIAID supports our efforts to further develop the next generation of our LAIV technology with the H7N9 strain.”

Influenza is a threat to public health. An estimated one billion cases of seasonal (epidemic) influenza occur annually worldwide, causing 20,000 to 36,000 excess deaths per year in the US. Influenza pandemics also have occurred four times in the past century; the most recent was the swine-origin H1N1 influenza pandemic in 2009. In March 2013, a novel avian influenza A(H7N9) virus that can cause severe illness in humans emerged in China. To date, there have been 141 confirmed cases of and 45 deaths from H7N9 human infection, with limited person-to-person transmission. If the H7N9 influenza virus acquires the ability to spread readily from person to person, the risk of an H7N9 pandemic will be much greater. Vaccines are the most important intervention in reducing the impact of influenza and are a key component of the World Health Organization (WHO) response and preparedness efforts for influenza strains that pose a pandemic threat.

Vivaldi is developing live attenuated influenza vaccines (LAIVs) with the potential for superior efficacy in preventing seasonal influenza and emerging pandemic influenza.