ILiAD Biotechnologies Publishes Phase 2b SUPER Trial Results for Intranasal Pertussis Vaccine Candidate BPZE1 in The Lancet Infectious Diseases
ILiAD Biotechnologies, Inc. (ILiAD), an advanced clinical-stage biotechnology company focused on preventing and treating diseases caused by Bordetella pertussis, has announced the publication of results from its Phase 2b SUPER (Stand Up to Pertussis) clinical trial in The Lancet Infectious Diseases. The randomized, double-blind, placebo- and active-comparator-controlled study evaluated BPZE1, a live attenuated intranasal pertussis vaccine candidate, in healthy children and adolescents aged 6 through 17 years.
The Phase 2b study provides clinical evidence that a single intranasal dose of BPZE1 can induce robust pertussis-specific immune responses in the nasal mucosa, including secretory immunoglobulin A (S-IgA), while maintaining a favorable safety profile. The trial also evaluated BPZE1 when administered alone and when given together with a tetanus-diphtheria-acellular pertussis (Tdap) booster vaccine.
According to ILiAD, the study met its primary immunogenicity endpoint by demonstrating significant induction of pertussis-specific nasal S-IgA. BPZE1 also met a key secondary objective by showing no interference with systemic immune responses generated by the co-administered Tdap vaccine.
The findings add to the clinical development program for BPZE1 and support further investigation of an intranasal approach to pertussis prevention, particularly because mucosal immunity may have an important role in limiting infection and transmission.
Addressing the Continuing Burden of Pertussis
Pertussis, commonly known as whooping cough, is a respiratory infection caused primarily by Bordetella pertussis. Although vaccination has substantially reduced the burden of severe disease, the pathogen continues to circulate globally.
The persistence of pertussis transmission presents an ongoing challenge for public health systems. Current vaccination approaches have primarily focused on preventing disease and reducing severe outcomes, while continued circulation of the bacterium highlights the importance of understanding how vaccination can generate immunity at the sites where respiratory pathogens initially encounter the body.
BPZE1 is being developed with an intranasal delivery approach intended to stimulate immune responses directly in the respiratory tract. The SUPER trial therefore examined nasal mucosal immunity in children and adolescents who had already received acellular pertussis-containing vaccines during infancy.
This population is particularly relevant to the development of new pertussis vaccination strategies because individuals who have previously completed infant vaccination schedules can continue to become infected and potentially contribute to transmission later in childhood and adolescence.
Phase 2b SUPER Trial Enrolled 366 Participants
The multicenter Phase 2b SUPER trial enrolled 366 participants across 16 clinical sites in the United Kingdom, Australia and Costa Rica.
Participants were healthy children and adolescents between 6 and 17 years of age who had received acellular pertussis-containing vaccines during infancy. The randomized, double-blind study included placebo and active comparator groups, allowing investigators to assess the immune response and safety profile associated with BPZE1 while also evaluating its compatibility with an existing Tdap booster vaccination.
A central objective was to determine whether BPZE1 could stimulate pertussis-specific immune responses within the nasal mucosa.
The study met its primary immunogenicity endpoint, demonstrating significant induction of pertussis-specific nasal secretory IgA following administration of BPZE1.
Secretory IgA is an important component of mucosal immunity. It is found at mucosal surfaces, including the respiratory tract, where it can contribute to immune defense against pathogens encountered through the nose and airways.
The induction of nasal S-IgA is therefore an important measure for an intranasal vaccine candidate because it provides information about the immune response generated at the site where respiratory infection begins.
Broad Nasal Mucosal Immune Response
ILiAD reported that a single intranasal dose of BPZE1 generated nasal mucosal immune responses against all Bordetella pertussis antigens tested in the study.
The finding is significant within the context of BPZE1’s development because the vaccine is designed to stimulate immunity through the nasal route rather than relying exclusively on systemic immune responses generated through traditional vaccination.
By inducing mucosal immunity, BPZE1 is being investigated as a potential approach that could address multiple stages of the infection process.
The company says the ultimate development goal is not only to prevent pertussis disease but also to explore whether BPZE1 could help prevent Bordetella pertussis infection and transmission.
The Phase 2b results do not establish that BPZE1 prevents transmission or infection in real-world populations, but the observed mucosal immune response provides clinical evidence supporting continued investigation of that potential.
Compatibility With Tdap Booster Vaccination
Another important component of the SUPER trial was the assessment of BPZE1 when administered alongside a Tdap booster.
Vaccination strategies may need to be incorporated into existing immunization programs rather than replace established vaccines outright. For that reason, determining whether a new vaccine candidate interferes with immune responses generated by an existing vaccine is an important part of clinical development.
In the SUPER trial, BPZE1 met its key secondary objective by demonstrating no interference with systemic immune responses induced by the co-administered Tdap vaccination.
This finding indicates that administration of BPZE1 alongside Tdap did not negatively affect the systemic immune responses evaluated in the study.
The combination of a nasal vaccine candidate with an established booster approach could potentially provide an additional strategy for strengthening protection against pertussis, although further clinical studies will be required to determine the effectiveness and appropriate use of such an approach.
Favorable Safety and Tolerability Profile
In addition to assessing immunogenicity, the SUPER trial evaluated the safety and tolerability of BPZE1.
The vaccine demonstrated a favorable safety profile, with minimal reactogenicity reported during the first seven days following vaccination.
Importantly, there were no vaccine-related serious adverse events, deaths or discontinuations reported in the study. Most adverse events were described as mild to moderate in severity.
The safety findings provide additional support for continued clinical development, particularly because BPZE1 is being investigated in children and adolescents.
Safety and tolerability are important considerations when evaluating vaccine candidates intended for use in generally healthy populations. The absence of vaccine-related serious adverse events in this Phase 2b study is therefore an important component of the overall clinical profile reported by ILiAD.
The study’s safety results, together with the observed nasal immune responses, contribute to the evidence supporting continued evaluation of BPZE1 in subsequent clinical development.
Expert Perspective on BPZE1’s Potential
Saul Faust, MBBS, PhD, Coordinating Investigator of the SUPER study, Professor of Pediatric Immunology and Infectious Diseases at the University of Southampton and Director of the National Institute for Health and Care Research (NIHR) Clinical Research Facility: Southampton, emphasized the continuing challenge posed by pertussis.
“Despite widespread vaccination, pertussis continues to circulate globally,” Faust said.
He noted that the immune and safety findings from the SUPER trial provide further support for investigating BPZE1 as an intranasal vaccine candidate.
“The robust BPZE1-induced nasal mucosal immune responses, non-interference with a current acellular pertussis vaccine, and favorable safety profile observed in this study further support the continued development of BPZE1 as a novel intranasal vaccine with the potential to address the shortcomings of current pertussis prevention,” Faust added.
His comments highlight the rationale behind pursuing a mucosal vaccination strategy in addition to established approaches.
Expanding Evidence in Previously Vaccinated Children
Stephanie Noviello, MD, Chief Medical Officer of ILiAD Biotechnologies, said publication of the SUPER results represents an important milestone for the BPZE1 program.
“The publication of the SUPER study results marks an important step in expanding our understanding of BPZE1’s potential in children and adolescents who previously received the acellular pertussis vaccine series, a population that continues to play an important role in pertussis transmission,” Noviello said.
The company also acknowledged the participants and research teams involved in conducting the multicenter study.
“We are deeply grateful to the children who participated in the study, their families and caregivers, and the investigators, study coordinators, and site personnel whose commitment made this research possible,” Noviello added.
The comments underscore the collaborative nature of vaccine development, particularly for pediatric clinical research involving multiple countries and clinical sites.
Potential Role of Mucosal Immunity in Pertussis Prevention
One of the distinguishing features of BPZE1 is its intranasal administration and the resulting focus on mucosal immune responses.
Traditional vaccination can generate systemic immune responses that play an important role in preventing severe disease. However, respiratory pathogens encounter mucosal surfaces before progressing to deeper tissues, creating interest in approaches that can stimulate immune defenses directly at these sites.
The SUPER trial’s demonstration of pertussis-specific nasal S-IgA following a single dose of BPZE1 provides evidence that the vaccine can generate the type of mucosal immune response being targeted by its development program.
The clinical implications of that response remain under investigation. While immunogenicity findings are an important component of vaccine development, additional studies are needed to determine how the immune responses translate into protection against infection, disease and transmission.
ILiAD is therefore positioning the Phase 2b findings as support for continued development rather than as definitive evidence of population-level effectiveness.
Next Steps for BPZE1 Development
The publication of the SUPER trial results in The Lancet Infectious Diseases adds peer-reviewed evidence to the clinical development program for BPZE1.
The study met its primary immunogenicity endpoint, demonstrating significant induction of nasal pertussis-specific S-IgA, while also meeting a key secondary objective related to compatibility with Tdap vaccination. The favorable safety profile observed in the trial further supports continued evaluation of the vaccine candidate.
The results are particularly relevant because the study involved children and adolescents who had already received acellular pertussis-containing vaccines in infancy, providing clinical data in a population that remains important to understanding ongoing pertussis circulation.
The authors concluded that the findings support continued development of BPZE1 as a potential next-generation pertussis vaccine. The longer-term development objective is to determine whether the vaccine can contribute not only to prevention of pertussis disease but also to reducing Bordetella pertussis infection and transmission among children and adults.
Further clinical research will be needed to establish the extent and durability of protection, evaluate BPZE1 across broader populations and determine its potential role alongside existing pertussis vaccination strategies.
For ILiAD Biotechnologies, the Phase 2b SUPER results represent an important step in advancing an intranasal approach to pertussis vaccination. The combination of robust nasal mucosal immune responses, compatibility with Tdap vaccination and a favorable safety profile provides a foundation for continued development as researchers seek new ways to address the persistent global circulation of pertussis.
About BPZE1
BPZE1 is a next-generation live-attenuated intranasal pertussis vaccine designed to induce comprehensive and durable protection against B. pertussis infection (colonization) and disease (whooping cough). BPZE1 is being developed to block B. pertussis from colonizing adult and school-age children’s nasal passages, to protect from whooping cough, and to potentially prevent transmission, including transmission to infants. While ILiAD is currently focused on developing a vaccine to directly protect adults and school-age children and to indirectly protect vulnerable infants, future development aims to immunize neonates directly. BPZE1 was developed at the Institut Pasteur de Lille (France) in the lab of Camille Locht and Nathalie Mielcarek.
About Pertussis
Pertussis (whooping cough) is a life-threatening disease caused by the highly contagious respiratory bacterium Bordetella pertussis. According to U.S. Centers for Disease Control and Prevention, each year pertussis affects approximately 16 million people globally, accounting for more than 150,000 deaths. Although estimated global vaccination coverage is 84%, current vaccines have failed to control epidemics. In addition, current vaccines do not fully protect infants under age 6 months, since primary immunization requires multiple injections, usually at 2, 4 and 6 months of age.
About ILiAD Biotechnologies
ILiAD Biotechnologies (http://www.iliadbio.com) is a privately held, advanced clinical stage biotechnology company dedicated to the prevention and treatment of human disease caused by Bordetella pertussis. The company is developing and exploring key technologies, working with leading scientists to overcome the limitations of current vaccines, investigating the impact of B. pertussis in a range of human disease, and is focused on validating its proprietary vaccines in human clinical trials.
About NIHR facilities in Southampton
The NIHR Clinical Research Facility: Southampton and NIHR Biomedical Research Centre: Southampton support the development and testing of new approaches to preventing, diagnosing and treating disease, helping innovative discoveries move more quickly into patient care. Together, they bring researchers, healthcare professionals, industry partners and patients together to deliver experimental medicine research and early-phase clinical studies. Both are partnerships between University Hospital Southampton NHS Foundation Trust and the University of Southampton, funded by the National Institute for Health and Care Research (NIHR).