Novavax Inc., a clinical-stage biotechnology company focused on catalysts that prevent a broad range of infectious diseases, recently released promising data about its flu vaccine candidate, NanoFlu. Novavax is developing NanoFlu to protect older adults from seasonal influenza. A preclinical study of the nanoparticle influenza vaccine candidate utilizing Novavax’ proprietary Matrix-M adjuvant suggests that it may be more effective than Fluzone High Dose based on antibody titers and neutralization of recent and historic influenza viruses.
The NanoFlu vaccine candidate is differentiated because it is a recombinant nanoparticle vaccine, genetically engineered from the hemagglutinin protein of the flu virus, which is distinct from inactivated flu vaccines that utilize egg-based manufacturing. The results of the study have been published in the journal Vaccine.
The Vaccine article describes the formulation of NanoFlu, based on the 2017-2018 World Health Organization recommended influenza strains. The study, conducted in ferrets, found that NanoFlu induced hemagglutination-inhibition (HAI) and microneutralizing (MN) antibodies against a broad range of influenza subtypes. In a head-to-head comparison against standard-dose and high-dose (HD) inactivated influenza vaccines in ferrets, NanoFlu elicited higher HAI and MN antibody responses exceeding those induced by the high-dose vaccine against recent (homologous) A(H3N2) by sevenfold, A(H1N1) by 26-fold, and B strain viruses by twofold. Additionally, NanoFlu induced superior protection in a ferret challenge model against a homologous and a 10-year-old drifted influenza strain spanning over a decade.
Ferrets are considered the gold-standard animal model for flu vaccines, so the promising results reported provide a strong rationale for the rapid initiation of a Phase 1/2 safety and immunogenicity clinical trial, with preliminary data expected by the end of 2017. Based on the potential for accelerated approval, Novavax could initiate a pivotal Phase 3 immunogenicity trial by the end of 2018.
“These data suggest that NanoFlu has the potential to elicit a broader, more robust immune response, resulting in greater protection than the market-leading licensed influenza vaccine in older adults, Sanofi’s Fluzone High-Dose. NanoFlu outperformed standard-dose Fluzone and Fluzone HD in HAI assays, an established surrogate marker of protection,” said Dr. Gregory Glenn, president of research and development for Novavax. “Further, these data suggest NanoFlu has the potential to address the problem of annual strain mismatch due to its ability to induce highly neutralizing antibodies against a broad range of influenza strains. These data show that NanoFlu provides improved protective responses to both the currently recommended influenza strains as well as drifted strains.”
“Novavax has over a decade of experience in developing both seasonal and pandemic influenza vaccine candidates. Based on the superior attributes of our nanoparticle-based vaccine candidates, we transitioned our influenza development activities to our nanoparticle vaccine platform,” said Stanley C. Erck, company president and CEO. “Our goal is to deliver a superior, differentiated vaccine to the greater than $3-billion global seasonal influenza commercial market.”
Novavax’s recombinant nanoparticles and Matrix-M saponin-based adjuvant technology, the key to the success of NanoFlu, are the foundation for what it sees as a groundbreaking innovation that improves global health through safe and effective vaccines. Saponin-based adjuvants act in part by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in the local lymph nodes. Thus, Matrix-M induces both a cell-mediated and an antibody-mediated immune response, which Novavax expects will be important in developing future vaccines. Matrix-M also increases the opportunity for an immune reaction with a longer duration, which could potentially reduce the number of vaccinations needed to gain optimal protection.
Influenza is a highly contagious infectious disease spreading around the world in a yearly outbreak, resulting in about three to five million cases of severe illness and about 250,000 to 500,000 deaths. According to the World Health Organization: "Every winter, tens of millions of people get the flu. Most are only ill and out of work for a week, yet others will develop life-threatening complications (such as pneumonia). Thus, while certainly having a major impact on productivity, influenza can be deadly, especially for the weak, young and old, or chronically ill. People over 65 years old, pregnant women, very young children and people of any age with chronic medical conditions are more likely to get complications from influenzas, such as pneumonia, bronchitis, sinus, and ear infections. The flu can also worsen chronic health problems. People with emphysema, chronic bronchitis or asthma may experience shortness of breath while they have the flu, and influenza may cause worsening of coronary heart disease or congestive heart failure.”