Systemic and mucosal immune responses following oral adenoviral delivery of influenza vaccine to the human intestine by radio controlled capsule

Abstract

There are several benefits of oral immunization including the ability to elicit mucosal immune responses that may protect against pathogens that invade through a mucosal surface. Our understanding of human immune biology is hampered by the difficulty in isolating mucosal cells from humans, and the fact that animal models may or may not completely mirror human intestinal immunobiology. In this human pharmacodynamic study, a novel adenovirus vector-based platform expressing influenza hemagglutinin was explored. We used radio-controlled capsules to deliver the vaccine to either the jejunum or the ileum. The resulting immune responses induced by immunization at each of the intestinal sites were investigated. Both intestinal sites were capable of inducing mucosal and systemic immune responses to influenza hemagglutinin, but ileum delivery induced higher numbers of antibody secreting cells of IgG and IgA isotypes, increased mucosal homing B cells, and higher number of vaccine responders. Overall, these data provided substantial insights into human mucosal inductive sites, and aided in the design and selection of indications that could be used with this oral vaccine platform.

Current state and challenges in developing oral vaccines

“…Vaccines using adenoviral vectors have targeted a wide range of some of the most challenging diseases, including HIV, influenza, rabies, botulism, dengue, SARS and Ebola [167–173]. They are able to generate robust cellular and humoral immune responses.…”

A multifaceted approach to RSV vaccination

“…Clinical trials are under way (NCT02830932). Although a vaccine using the same platform was tested for influenza in mouse, ferrets, and in humans 48,79,80 showing promising results, up to date no preclinical studies using the RSV vaccine have been reported.…”

Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial

“…Immunophenotyping was performed on cryopreserved PBMCs as described previously (16). Data were collected on a BD LSR II cytometer using FACS DIVA software and analyzed using FlowJo software (version 10.2).…”

“…In their study, virus-specific ASCs that expressed the α4β7 integrin were used as a biomarker for mucosal immunity, since α4β7 is involved in selective B cell homing to mucosal intestinal tissues. The Vaxart vector approach has also been shown to induce IgA ASCs and α4β7-expressing B cells (16) in humans, suggesting that this vaccine platform is capable of initiating an intestinal immune response that could be especially advantageous for deterring a pathogen that infects the intestinal mucosa.…”

“…The orally administered vaccine tablet platform is well tolerated and generates robust neutralizing antibody responses to influenza as well as mucosal immune responses (16,17). In poliovirus human vaccine studies, Dey et al have shown that a virus-specific antibody-secreting cell (ASC) response can be used as a measure of mucosal immunity induction following oral vaccination against an enteric pathogen (18).…”