Thread by @Novavax

We’re proud to announce the publication of our successful Phase 3 trial of NanoFlu™, our seasonal quadrivalent Nanoparticle #Influenza #Vaccine (#qNIV) candidate, in @TheLancetInfDis. Let’s dig into why it matters: thelancet.com/journals/lanin…

Thread:

According to @CDC, “on average, about 8% of the U.S. population gets sick from #flu each season.” There is an urgent need for improved flu #vaccines, particularly for older adults (>age 65), who bear higher disease burden. cdc.gov/flu/about/keyf…

Coverage of existing flu vaccines is >60% in the US, but recent flu seasons have shown vaccine effectiveness may be just 10-13% for one virus strain (A/H3N2) in older adults. ncbi.nlm.nih.gov/pmc/articles/P…

This strain accounts for most disease & evolves most rapidly. Seasonal flu vaccines typically cover 2 A types of the influenza virus and 1 or 2 B types. cdc.gov/flu/about/viru…

Further, existing flu vaccines have shown 3 other limitations: 1) induction of antibody responses that may not cross-protect against increasingly frequent antigenic drift of flu viruses; pubmed.ncbi.nlm.nih.gov/31102401

2) lower immune responses in older adults #immunosenescence;

3) reliance on egg-based vaccine production methods, which require adaptations that may negatively impact vaccine performance. New tools are needed. nejm.org/doi/full/10.10…

To address these challenges, we developed a new approach: #NanoFlu (qNIV), formulated with our unique, saponin-based Matrix-M™ adjuvant. This #flu vaccine is produced in our recombinant Sf9 cell-based system.

This study compared NanoFlu to a licensed, standard dose quadrivalent inactivated influenza vaccine (IIV4) in older US adults, before the 2019-2020 flu season. 2654 participants were randomized 1:1 to NanoFlu or IIV4.

The primary objectives: describe safety & demonstrate non-inferior immunogenicity of NanoFlu to IIV4, 28 days after immunization, using HAI antibody responses assayed with classic egg-based reagents.

We also aimed to describe the immune response using a wild-type HAI assay against 4 vaccine strains, 6 heterologous A/H3N2 strains & 1 heterologous B strain.

Another goal was to evaluate cell-mediated immune responses to NanoFlu.

Results: NanoFlu showed immunologic non-inferiority to IIV4 against 4 vaccine-homologous strains & statistically improved responses for 3 of the 4 vaccine-homologous strains using egg-based HAI assay. Primary objective: Met

NanoFlu showed an acceptable safety profile.

When wild type HAI antibody responses were assessed (more biologically relevant than egg-based assays), NanoFlu fared even better:

At 28 days after vaccination, NanoFlu showed 2.1-5.6x increases in titers, compared to 1.6-3.4x increases for IIV4.

NanoFlu also induced broader antibody responses: significant improvements of 34-46% over IIV4 against 6 heterologous A/H3N2 strains, and a 23% improvement against a heterologous B strain.

In looking at cell-mediated immunity (#CMI), NanoFlu showed a substantially greater induction (126-189% higher) of IFNγ & antigen-specific polyfunctional CD4+ T-cell (memory) responses vs IIV4.

Further, the entire distribution of CMI responses was shifted substantially & symmetrically to the right with NanoFlu, compared to a more modest & asymmetrical shift with IIV4.

The above results also suggest that potent CMI responses can be induced even in usual low responders.

Summary of 4 key findings: NanoFlu showed non-inferiority to IIV4 & met its primary objective.

Antibody responses were qualitatively broader & quantitatively greater than IIV4 against both homologous strains, and heterologous A/H3N2 and B strains.

NanoFlu significantly outperformed IIV4 in the induction of memory and total CD4+ T-cells. NanoFlu was also well tolerated.

Why it matters: Higher titers may mean more protection. Broader responses may mean protection against antigenic drift during and between flu seasons. Memory responses may improve durability of protection.

Novavax is encouraged by these findings and looks forward to the continued development of our candidates. We recently launched a Phase 1/2 study that combines NanoFlu with our COVID-19 vaccine candidate.