Long-term immunogenicity and safety of a non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine: 4-year follow-up of a phase 1 multicentre trial

Smedt, Philippe De; Leroux‐Roels, Geert; Vandermeulen, Corinne; Tasciotti, Annaelisa; Maro, Gennaro Di; Dozot, Marie; Casula, D; Annaratone, Margherita; Riccucci, Daniele; Arora, Ashwani Kumar

doi:10.1016/j.jvacx.2021.100124

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…The safety and reactogenicity profile of the NTHi-Mcat vaccine was consistent with previous studies. 5 , 6 , 15 , 16 Reactogenicity was similar in the study groups who received NTHi-Mcat after RZV and the group who received NTHi-Mcat vaccine alone and there were few severe reactogenicity events. Unsolicited AEs occurred with similar frequency in all study groups and were mainly mild or moderate in severity.…”

Section: Discussionmentioning

confidence: 76%

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Immunogenicity and safety of the non-typable Haemophilus influenzae – Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Galgani¹,

Põder²,

Jõgi

et al. 2023

Human Vaccines & Immunotherapeutics

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A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50–80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.

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Section: Discussionmentioning

confidence: 76%

“…Similar robust humoral immune responses have been observed in previous studies of the vaccine when administered alone. 5 , 6 , 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of the non-typable Haemophilus influenzae – Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Galgani¹,

Põder²,

Jõgi

et al. 2023

Human Vaccines & Immunotherapeutics

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“…However, more recent analysis indicates that the sequence diversity among gonococcal strains is more restricted, so that a TbpB-based gonococcal vaccine would have a limited impact on 'commensal' Neisseria species. A TbpB-based vaccine against H. influenzae would have the additional advantage of also targeting bacteria that lack a polysaccharide capsule, including the non-typeable H. influenzae (NTHi) (Novotny et al, 2017;De Smedt et al, 2021), that cause otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults (Murphy, 2015). It would also address the issue of the increasing incidence of meningitis caused by other capsular types of H. influenzae (Ulanova and Tsang, 2009).…”

Section: Discussionmentioning

confidence: 99%

Insights from targeting transferrin receptors to develop vaccines for pathogens of humans and food production animals

Ewasechko

Chaudhuri²,

Schryvers³

2023

Front. Cell. Infect. Microbiol.

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While developing vaccines targeting surface transferrin receptor proteins in Gram-negative pathogens of humans and food production animals, the common features derived from their evolutionary origins has provided us with insights on how improvements could be implemented in the various stages of research and vaccine development. These pathogens are adapted to live exclusively on the mucosal surfaces of the upper respiratory or genitourinary tract of their host and rely on their receptors to acquire iron from transferrin for survival, indicating that there likely are common mechanisms for delivering transferrin to the mucosal surfaces that should be explored. The modern-day receptors are derived from those present in bacteria that lived over 320 million years ago. The pathogens represent the most host adapted members of their bacterial lineages and may possess factors that enable them to have strong association with the mucosal epithelial cells, thus likely reside in a different niche than the commensal members of the bacterial lineage. The bacterial pathogens normally lead a commensal lifestyle which presents challenges for development of relevant infection models as most infection models either exclude the early stages of colonization or subsequent disease development, and the immune mechanisms at the mucosal surface that would prevent disease are not evident. Development of infection models emulating natural horizontal disease transmission are also lacking. Our aim is to share our insights from the study of pathogens of humans and food production animals with individuals involved in vaccine development, maintaining health or regulation of products in the human and animal health sectors.

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“…A multi-component NTHi vaccine consisting of a free recombinant PD and a recombinant fusion protein PE-PilA was tested in a phase 1 clinical trial in healthy adults (NCT01657526), with a good safety profile and acceptable reactogenicity ( Leroux-Roels et al, 2016 ). A further development added the Mcat antigen UspA2 to this combination, to test a multi-component vaccine in two-dose and three-dose phase 1 and 2 clinical trials, showing promising safety and immunogenicity profiles in healthy adults and adults aged 50–71 with a history of smoking ( De Smedt et al, 2021 ; Galgani et al, 2022 ).…”

Section: Vaccines Against Ommentioning

confidence: 99%

Otitis media: recent advances in otitis media vaccine development and model systems

Zahid,

Wilson,

Grice

et al. 2024

Front. Microbiol.

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Otitis media is an inflammatory disorder of the middle ear caused by airways-associated bacterial or viral infections. It is one of the most common childhood infections as globally more than 80% of children are diagnosed with acute otitis media by 3 years of age and it is a common reason for doctor’s visits, antibiotics prescriptions, and surgery among children. Otitis media is a multifactorial disease with various genetic, immunologic, infectious, and environmental factors predisposing children to develop ear infections. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common culprits responsible for acute otitis media. Despite the massive global disease burden, the pathogenesis of otitis media is still unclear and requires extensive future research. Antibiotics are the preferred treatment to cure middle ear infections, however, the antimicrobial resistance rate of common middle ear pathogens has increased considerably over the years. At present, pneumococcal and influenza vaccines are administered as a preventive measure against otitis media, nevertheless, these vaccines are only beneficial in preventing carriage and/or disease caused by vaccine serotypes. Otitis media caused by non-vaccine serotype pneumococci, non-typeable H. influenza, and M. catarrhalis remain an important healthcare burden. The development of multi-species vaccines is an arduous process but is required to reduce the global burden of this disease. Many novel vaccines against S. pneumoniae, non-typeable H. influenza, and M. catarrhalis are in preclinical trials. It is anticipated that these vaccines will lower the disease burden and provide better protection against otitis media. To study disease pathology the rat, mouse, and chinchilla are commonly used to induce experimental acute otitis media to test new therapeutics, including antibiotics and vaccines. Each of these models has its advantages and disadvantages, yet there is still a need to develop an improved animal model providing a better correlated mechanistic understanding of human middle ear infections, thereby underpinning the development of more effective otitis media therapeutics. This review provides an updated summary of current vaccines against otitis media, various animal models of otitis media, their limitations, and some future insights in this field providing a springboard in the development of new animal models and novel vaccines for otitis media.

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Long-term immunogenicity and safety of a non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine: 4-year follow-up of a phase 1 multicentre trial

Cited by 6 publications

References 35 publications

Immunogenicity and safety of the non-typable Haemophilus influenzae – Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Immunogenicity and safety of the non-typable Haemophilus influenzae – Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

Insights from targeting transferrin receptors to develop vaccines for pathogens of humans and food production animals

Otitis media: recent advances in otitis media vaccine development and model systems

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