1947. Influenza Vaccination via Oral Tablet is Protective and Induces a Unique Mucosal Immune Response

Abstract

BackgroundOral vaccines delivered as tablets offer several advantages over traditional injection-based vaccines including ease of distribution and administration as well as temperature-stable formulation options. Oral vaccination is also advantageous because it directly induces a strong mucosal response, which is thought to be critical for preventing future infections. Here we present results from a phase II clinical challenge study comparing efficacy of an oral recombinant adenovirus-based vaccine expressing hemagluttinin (HA) from A/California 04/09 to that of a commercial injectable quadrivalent (QIV) influenza vaccine.MethodsIn this 2016–2017 clinical trial (NCT02918006), subjects were immunized with either oral vaccine, QIV, or placebo and then challenged 90 days post-immunization with wildtype influenza A H1 virus to measure vaccine efficacy and durability. Protection was assessed by measuring changes in HAI titres, microneutralization, and IgA/IgG ASC assays. Additionally, exploratory flow cytometry evaluated quantitative and qualitative aspects of immunogenicity including markers of activation and mucosal homing on B cells. Analysis was performed on days 0 and 7 post-immunization and 0 and 6 days post-viral challenge. Plasmablasts sorted from PBMCs were then isolated for genomic DNA and sequenced for heavy chain receptor sequencing using NGS analysis.ResultsOf the subjects immunized with Vaxart’s oral tablet vaccine, 48% were protected. QIV, by comparison, protected 38% of immunized individuals. Only 37% of Vaxart subjects developed influenza infection compared with 44% of QIV subjects and 71% of placebo subjects. While both vaccines induced a humoral immune response, FACS analysis and NGS revealed that Vaxart subjects had more activated plasmablasts expressing surface mucosal homing markers and a more diverse B cell population than QIV subjects.ConclusionVaxart’s oral influenza tablet vaccine protected against influenza infection as well or better than injectable QIV. However, the mechanism of protection appears to be unique to the route of immunization; oral immunization allows for specific homing of influenza specific B cells to sites of infection and produces a more diverse antibody repertoire.Disclosures N. Kolhatkar, Vaxart, Inc.: Employee, Salary. K. Gottlieb, Vaxart, Inc.: Employee, Salary. K. Kasparek, Vaxart, Inc.: Employee, Salary. K. Hodgson, Vaxart, Inc.: Employee, Salary. S. Tucker, Vaxart, Inc: Employee, Salary. D. Liebowitz, Vaxart, Inc.: Employee and Investigator, Salary.

A Decade in Review: A Systematic Review of Universal Influenza Vaccines in Clinical Trials during the 2010 Decade

“…Vaccination resulted in mild side effects at similar rates to the placebo group. Phase 2 clinical trial participants were immunized with VXA-A1.1 or the seasonal QIV vaccine and then challenged with an H1N1 influenza strain [ 87 ]. Vaccination with VXA-A1.1 resulted in 48% protection compared to 38% with the seasonal vaccine.…”

Adenoviral vector‐based platforms for developing effective vaccines to combat respiratory viral infections

“…Another promising randomised, single‐dose, Phase II challenge study (clinical trial NCT02918006) utilised a dsRNA‐adjuvanted HAd5 bearing the H1N1 HA gene (VXA‐A1.1) via oral administration. 201 Participants ( n = 180) in three groups received either VXA‐A1.1 orally, licensed quadrivalent inactivated vaccine (QIV) by the i.m. route, or placebo, and challenged three months post‐immunisation with a matched A/H1N1 influenza virus.…”

“…VXA‐A1.1 exhibited 48% protection compared with 38% protection with QIV. 201 In a randomised, double‐blinded, dose–escalation Phase II clinical study, the immunogenicity and efficacy of a HAd5 carrying H1HA (NasoVAX) were evaluated in healthy participants aged 18–49 years. It was found to be well tolerated and induced potent humoral immunity measured by HI (NCT03232567).…”

Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines

“…HAd5 vector-based influenza vaccines have been used in several clinical trials [ 96 , 97 , 98 , 99 , 100 ] ( Table 2 ). A phase II randomized influenza A challenge study (clinical trial NCT02918006) used the oral administration of an H1N1 HA HAd5 vector vaccine and a dsRNA adjuvant (VXA-A1.1) [ 101 ]. Healthy adult volunteers with undetectable or low preexisting antibodies to the H1N1 pdm09-like virus were chosen.…”