Recombinant truncated E protein as a new vaccine candidate against nontypeable H. influenzae: Its expression and immunogenic evaluation

Behrouzi, Ava; Bouzari, Saeid; Vaziri, Farzam; Fateh, Abolfazl; Afrough, Parviz; Motlagh, Atefeh Davoudi Vijeh

doi:10.1016/j.micpath.2017.07.025

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…Since the 2015 ISOM report, NTHi antigen discovery and refinement has predominated the literature with several novel observations and new candidate antigens [46][47][48][49]. Recombinant Protein D, truncated Protein E, and a Protein E-D fusion protein showed that immunogenicity in mice and antibodies were bactericidal and opsonophagocytic in vitro [50][51][52][53]. Among surfaceexposed proteins identified as essential for NTHi survival, antibodies against Hel1 and Hel2 prevented bacteremia in a rat model [54].…”

Section: Preclinical Studies Of New Vaccines Against Ommentioning

confidence: 99%

“…While parenteral immunization routes (subcutaneous and intramuscular) are the mainstay approach to assess the immunogenicity and efficacy of most preclinical and clinical vaccine candidates [50][51][52][53][54][55][56]81], greater emphasis has more recently been placed on alternative immunization regimens for preventing otopathogen colonization or OM. Herein we provide an update on alternative approaches being explored for delivery of novel OM vaccines.…”

Section: Novel Vaccine Development Approaches Against Ommentioning

confidence: 99%

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Panel 8: Vaccines and immunology

Alderson

Murphy

Pelton

et al. 2020

International Journal of Pediatric Otorhinolaryngology

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Section: Preclinical Studies Of New Vaccines Against Ommentioning

confidence: 99%

Section: Novel Vaccine Development Approaches Against Ommentioning

confidence: 99%

Panel 8: Vaccines and immunology

Alderson

Murphy

Pelton

et al. 2020

International Journal of Pediatric Otorhinolaryngology

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“…The host complement system is further dampened by the plasmin that results from the binding of PE to plasminogen (24). PE has recently been proposed to be a relevant NTHi vaccine antigen (25). PilA, the second antigen of the fusion protein, is the major subunit of type IV pili (Tfp) (26).…”

Section: Introductionmentioning

confidence: 99%

A Protein E-PilA Fusion Protein Shows Vaccine Potential against Nontypeable Haemophilus influenzae in Mice and Chinchillas

et al. 2019

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PE-PilA is a fusion protein composed of immunologically relevant parts of protein E (PE) and the majority subunit of the type IV pilus (PilA), two major antigens of nontypeable Haemophilus influenzae (NTHi). Here we report on the preclinical evaluation of PE-PilA as a vaccine antigen. The immunogenic potential of the PE and PilA within the fusion was compared with that of isolated PE and PilA antigens. When injected intramuscularly into mice, the immunogenicity of PE within the fusion was equivalent to that of isolated PE, except when it was formulated with alum. In contrast, in our murine models PilA was consistently found to be more immunogenic as a subentity of the PE-PilA fusion protein than when it was injected as an isolated antigen. Following immunization with PE-PilA, anti-PE antibodies demonstrated the same capacity to inhibit the binding of PE to vitronectin as those induced after PE immunization. Likewise, PE-PilA-induced anti-PilA antibodies inhibited the formation of NTHi biofilms and disrupted established biofilms in vitro. These experiments support the immunogenic equivalence between fused PE-PilA and isolated PE and PilA. Further, the potential of PE-PilA immunization against NTHi-induced disease was evaluated. After intranasal NTHi challenge, colonization of the murine nasopharynx significantly dropped in animals formerly immunized with PE-PilA, and in chinchillas, signs of otitis media were significantly reduced in animals that had received anti-PE-PilA antibodies. Taken together, our data support the use of PE-PilA as an NTHi vaccine antigen.

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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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Recombinant truncated E protein as a new vaccine candidate against nontypeable H. influenzae: Its expression and immunogenic evaluation

Cited by 3 publications

References 35 publications

Panel 8: Vaccines and immunology

Panel 8: Vaccines and immunology

A Protein E-PilA Fusion Protein Shows Vaccine Potential against Nontypeable Haemophilus influenzae in Mice and Chinchillas

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

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