Related Experiment Video
Updated: Oct 22, 2025
Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
Published on: December 19, 2020
UspA2 is a cross-protective Moraxella catarrhalis vaccine antigen
Carine Ysebaert1, Cindy Castado1, Marie-Cécile Mortier1
1GSK, Rixensart, Belgium.
Abstract:
Moraxella catarrhalis (Mcat) is a key pathogen associated with exacerbations of chronic obstructive pulmonary disease (COPD) in adults and playing a significant role in otitis media in children. A vaccine would help to reduce the morbidity and mortality associated with these diseases. UspA2 is an Mcat surface antigen considered earlier as vaccine candidate before the interest in this molecule vanished due to sequence variability. However, the observation that some conserved domains are the target of bactericidal antibodies prompted us to reconsider UspA2 as a potential vaccine antigen. We first determined its prevalence among the COPD patients from the AERIS study, as the prevalence of UspA2 in a COPD-restricted population had yet to be documented. The gene was found in all Mcat isolates either as UspA2 or UspA2H variant. The percentage of UspA2H variant was higher than in any report so far, reaching 51%. A potential link between the role of UspA2H in biofilm formation and this high prevalence is discussed. To study further UspA2 as a vaccine antigen, recombinant UspA2 molecules were designed and used in animal models and bactericidal assays. We showed that UspA2 is immunogenic and that UspA2 immunization clears Mcat pulmonary challenge in a mouse model. In a serum bactericidal assay, anti-UspA2 antibodies generated in mice, guinea pigs or rabbits were able to kill Mcat strains of various origins, including a subset of isolates from the AERIS study, cross-reacting with UspA2H and even UspA1, a closely related Mcat surface protein. In conclusion, UspA2 is a cross-reactive Mcat antigen presenting the characteristics of a vaccine candidate.
Insights
A potential vaccine targeting the Moraxella catarrhalis (Mcat) UspA2 antigen shows promise. Antibodies generated against UspA2 effectively killed various Mcat strains, suggesting its viability as a cross-reactive vaccine candidate for COPD and otitis media.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Moraxella catarrhalis (Mcat) is a significant pathogen causing COPD exacerbations and childhood otitis media.
- UspA2, an Mcat surface antigen, was previously overlooked as a vaccine candidate due to sequence variability.
- Conserved domains of UspA2 are targets of bactericidal antibodies, prompting renewed interest.
Purpose of the Study:
- To assess the prevalence of UspA2 and its variants in M. catarrhalis isolates from COPD patients.
- To evaluate the immunogenicity and efficacy of UspA2 as a vaccine antigen in preclinical models.
Main Methods:
- Prevalence study of UspA2/UspA2H variants in M. catarrhalis isolates from the AERIS COPD cohort.
- Production of recombinant UspA2 proteins.
- Immunization of animal models (mice, guinea pigs, rabbits) with UspA2.
- Assessment of anti-UspA2 antibody bactericidal activity in vitro and protection in a mouse pulmonary challenge model.
Main Results:
- The UspA2 gene was present in all M. catarrhalis isolates, with the UspA2H variant found at a higher prevalence (51%) than previously reported.
- Recombinant UspA2 was immunogenic, eliciting antibodies capable of killing diverse M. catarrhalis strains in serum bactericidal assays.
- UspA2 immunization conferred protection against M. catarrhalis pulmonary challenge in mice.
- Generated antibodies showed cross-reactivity with UspA2H, UspA1, and clinical isolates from the AERIS study.
Conclusions:
- UspA2 is a prevalent and cross-reactive antigen in M. catarrhalis.
- UspA2 demonstrates strong potential as a vaccine candidate to combat M. catarrhalis-associated diseases like COPD exacerbations and otitis media.
