Human immune responses elicited by an intranasal inactivated H5 influenza vaccine

Abstract

Intranasally administered influenza vaccines could be more effective than injected vaccines, because intranasal vaccination can induce virus-specific immunoglobulin A (IgA) antibodies in the upper respiratory tract, which is the initial site of infection. In this study, immune responses elicited by an intranasal inactivated vaccine of influenza A(H5N1) virus were evaluated in healthy individuals naive for influenza A(H5N1) virus. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy vinyl polymer, had a notable impact on the induction of nasal IgA antibody responses but not on serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific Th cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against influenza A(H5N1) viruses and ---This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Broadly Neutralizing Antibodies for Influenza: Passive Immunotherapy and Intranasal Vaccination

“…Several conserved HA targets have been identified (e.g., fusion peptides in the stalk domain), and many bnAbs are proceeding to clinical trials [ 14 ]. There are also ongoing clinical trials of intranasal vaccinations with inducible neutralizing pIgAs against HA to achieve cross-protection [ 105 ]. However, it is difficult to obtain HA2 stalk-specific antibodies with natural infections or conventional vaccinations.…”

“…Ichinohe et al demonstrated another effective adjuvant, a synthetic double-stranded RNA (dsRNA) polyriboinosinic polyribocytidylic acid (poly (I:C)) for intranasal vaccination [ 103 ]. Clinical studies have also suggested that secretory pIgAs, generated in response to inactivated nasally administered vaccine, play a significant role in providing protection from heterologous influenza viruses [ 104 , 105 ]. An intranasally delivered inactivated vaccine could be valuable in promoting some of the favorable immune responses elicited by LAIVs, without the risk of live virus to immunocompromised individuals.…”

An influenza HA stalk reactive polymeric IgA antibody exhibits anti-viral function regulated by binary interaction between HA and the antibody

“…This non-interventional study was performed using residual peripheral blood mononuclear cells collected from nine vaccinated healthy adult volunteers participating in previous interventional clinical trials for an intranasal inactivated influenza vaccine (Clinical trial registry: UMIN000008279 [ 39 ]). The study was conducted with the approval of the medical research ethics committee of the National Institute of Infectious Diseases for the use of human subjects, Tokyo, Japan (no.…”

“…920), and all participants provided written informed consent via an ethics committee-approved form. The primary outcome of the interventional clinical trial is reported separately [ 39 ]. Participants in the interventional clinical trial received three intranasal vaccinations with a monovalent WIV vaccine (45 μg HA/500 μl).…”

Local Nasal Response Against COVID-19: Debate Regarding the Absence of Nasal Inflammatory Symptoms

“…Intranasal vaccines have been developed, and the application of intranasal H5 influenza vaccine has been shown to not only produce local secretory IgA but also to induce IgG in serum. 10 Nasal inflammatory symptoms may be more important than previously thought. The absence of nasal inflammation allows the virus to replicate effectively and rapidly in the URT.…”