Airway Delivery of an Adenovirus-Based Ebola Virus Vaccine Bypasses Existing Immunity to Homologous Adenovirus in Nonhuman Primates

Abstract

b Anti-adenovirus serotype 5 antibodies are capable of neutralizing adenovirus serotype 5-based vaccines. In mice and guinea pigs, intranasal delivery of adenovirus serotype 5-based vaccine bypasses induced adenovirus serotype 5 preexisting immunity, resulting in protection against species-adapted Ebola virus challenge. In this study, nonhuman primates were vaccinated with adenovirus serotype 5-based vaccine either intramuscularly or via the airway route (intranasally/intratracheally) in the presence or absence of adenovirus serotype 5 preexisting immunity. Immune responses were evaluated to determine the effect of both the vaccine delivery route and preexisting immunity before and after a lethal Ebola virus (Zaïre strain Kikwit 95) challenge. Intramuscular vaccination fully protected nonhuman primates in the absence of preexisting immunity, whereas the presence of preexisting immunity abrogated vaccine efficacy and resulted in complete mortality. In contrast, the presence of preexisting immunity to adenovirus serotype 5 did not alter the survival rate of nonhuman primates receiving the adenovirus serotype 5-based Ebola virus vaccine in the airway. This study shows that airway vaccination with adenovirus serotype 5-based Ebola virus vaccine can efficiently bypass preexisting immunity to adenovirus serotype 5 and induce protective immune responses, albeit at lower efficacy than that using an intramuscular vaccine delivery route.

mAbs and Ad-Vectored IFN-α Therapy Rescue Ebola-Infected Nonhuman Primates When Administered After the Detection of Viremia and Symptoms

“…In these studies, Ad-IFN was administered through a single intramuscular injection per regimen to conveniently ensure full delivery of the formulation in an animal species that cannot inhale on demand. However, Ad-IFN is intended for delivery in the airway from a nasal spray, a delivery route that was recently shown to overcome existing immunity to homologous adenovirus in rodents and NHPs (19,20). Surviving animals across the different groups exhibited robust EBOVspecific B and T cell responses after challenge.…”

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

“…It may be that the Ad5-PAopt-and rPA-immunized rats produced different subtypes of antibodies or that the cellular immune response in the Ad5-PAopt-immunized rats contributed to the protection. Studies from our group and others have demonstrated that intranasal vaccination with Ad5-based vaccines can bypass PEI (27,29). There, we observed that compared to intranasal immunization, even in the presence of intranasal anti-Ad5 PEI, the intramuscular injection induced effective immune responses to protect rats from anthrax LT challenge in a relatively short time.…”

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease

“…Intranasal vaccination was observed as an effective vaccine delivery route in the presence of systemic or even mucosal pre-existing immunity to the Ad5 vector in guinea pigs [95], and use of hydrogel was found to be safe and effective as a delivery system for nasal immunization [96]. Of note, airway vaccination with an Ad5-based EBOV vaccine could efficiently bypass pre-existing immunity to Ad5 and induce protective immune responses in NHPs [97,98]. Altogether, the available data have shown great potential for adenovirus-based vaccines to be licensed in the future.…”