|Vivaldi is addressing the compelling need for more effective influenza vaccines with new-generation live attenuated influenza vaccines
(LAIVs) based on the biology of influenza nonstructural protein 1 (NS1). Vivaldi's clinical-stage vaccine candidates and LAIV technology platform provide a new
vaccine approach with the potential for superior safety and efficacy in the prevention of seasonal and pandemic influenza.
Vivaldi's deltaFLU LAIV is the company's lead vaccine candidate. deltaFLU LAIVs have been evaluated in three Phase 1 and one Phase 1/2 randomized, double-blind,
placebo-controlled clinical trials. These studies show that deltaFLU LAIVs have the potential to provide broad cross-protection, and more effective and durable immunity
against seasonal and pandemic influenza strains compared to currently available vaccines.
Conventional inactivated influenza vaccines lack effectiveness when the vaccine strains are not well matched to circulating influenza strains, as is often the case.
deltaFLU LAIVs have the potential to provide cross-protection against unmatched strains. Clinical studies show that deltaFLU LAIVs stimulate cross-neutralizing serum
antibodies against unmatched influenza strains. Preclinical studies in animal models show that deltaFLU LAIVs provide cross-protection when vaccinated animals are challenged
with unmatched strains. These findings indicate the potential for deltaFLU LAIVs to cross-protect against a broad range of circulating influenza strains, a significant advantage
over licensed vaccines.
Vivaldi develops deltaFLU LAIVs using proprietary reverse genetics and plasmid rescue technologies to delete the gene encoding influenza nonstructural protein 1 (NS1). These
deltaFLU vaccine strains lacking NS1 are safely attenuated and immunogenic.
NS1 is essential for influenza virus replication in man. Because deltaFLU LAIVs lack NS1, they are replication-deficient. Administered as a nasal spray, deltaFLU vaccine strains
undergo only an abortive replication cycle; they lack the ability to form infectious progeny viruses. deltaFLU strains are not shed by the recipient, and are not transmitted to other
individuals. These characteristics make deltaFLU LAIVs safe.
NS1 enables disease-causing influenza viruses to counteract the host interferon response. Lacking NS1, deltaFLU strains induce the recipient's immune system to produce high levels of interferon, achieving a natural adjuvant
effect that activates antibody-producing B cells and T cells. This unique mode of action enables deltaFLU LAIVs to induce a potent immune response.
deltaFLU LAIVs are produced in Vero cell culture, an advanced vaccine production platform that provides important improvements versus traditional egg-substrate vaccine manufacturing
technologies in terms of speed, reliability, efficiency, and cost.
Vivaldi plans to undertake a Phase 2 study of a monovalent deltaFLU LAIV in healthy adult volunteers to evaluate the ability of deltaFLU LAIV to provide protection against an unmatched
(heterologous) influenza strain. The study will be a randomized, double-blind, placebo-controlled challenge study to demonstrate safety, immunogenicity, and protective efficacy of the
deltaFLU LAIV against heterologous challenge, and to show statistically significant improvements in efficacy compared with a conventional inactivated vaccine ("flu shot").
Vivaldi also is planning a Phase 2 study of its quadrivalent deltaFLU LAIV candidate with the goal of demonstrating improved safety and greater protection against seasonal influenza in children. Vivaldi plans to carry out the Phase 2 pediatric clinical program in children age 6 months to 11 years. Based on successful clinical studies, Vivaldi will seek initial licensure for quadrivalent deltaFLU LAIV for seasonal influenza for individuals age 6 months and older, and subsequent licensure covering adolescents, adults, and seniors age 65 and older.
Vivaldi's VB126 LAIV platform is based on attenuated influenza strains with a precise truncation in the gene for influenza nonstructural protein 1 (NS1), achieved using proprietary reverse
genetics and plasmid rescue technologies. Preclinical evaluations demonstrate that VB126 LAIVs are safely attenuated, induce robust antigen-specific antibody titers in the absence of replication,
and provide protection from influenza infection.
Vivaldi successfully completed a Cooperative Research and Development Agreement (CRADA) with the National Institute of Allergy and Infectious Diseases (NIAID) for preclinical development
of a VB126 LAIV against H7N9, an influenza strain with pandemic potential. Under the CRADA Vivaldi generated a Phase 1-ready vaccine candidate that can be readily manufactured to commercial
standards, with preclinical data to support clinical trials in volunteers.
Vivaldi's LAIV technology is well suited for vaccines for pandemic preparedness. The novel mode of action of Vivaldi's LAIVs provides potent immunogenicity, and the self-adjuvanting
effect is antigen-sparing, without the need for vaccine adjuvants. Nasal spray administration is amenable to self-administration and mass use. Vivaldi's proprietary reverse genetics and
plasmid rescue technologies enable a rapid response to an emerging pandemic strain; new vaccine strains can be prepared in a week. Vero cell culture production enables the capacity and
speed required to produce vaccines for pandemic preparedness.