Anti-EF-Tu IgG titers increase with age and may contribute to protection against the respiratory pathogen Haemophilus influenzae.

Marta Brant,Anna Rudin,Derek Hood,Ravinder Kaur,Kristian Riesbeck,Oskar Thofte,Yu‐Ching Su

doi:10.1002/eji.201847871

Abstract

Non‐typeable Haemophilus influenzae (NTHi) is a pathogen that commonly colonizes the nasopharynx of preschool children, causing opportunistic infections including acute otitis media (AOM). Patients suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized with NTHi and occasionally suffer from exacerbations by the bacterium leading to increased morbidity. Elongation‐factor thermo unstable (EF‐Tu), a protein critical for bacterial protein synthesis, has been found to moonlight on the surface of several bacteria. Here, we show that antibodies against NTHi EF‐Tu were present in children already at 18 months of age, and that the IgG antibody titers increased with age. Children harboring NTHi in the nasopharynx also displayed significantly higher IgG concentrations. Interestingly, children suffering from AOM had significantly higher anti‐EF‐Tu IgG levels when NTHi was the causative agent. Human sera recognized mainly the central and C‐terminal part of the EF‐Tu molecule and peptide‐based epitope mapping confirmed similar binding patterns for sera from humans and immunized mice. Immunization of BALB/c and otitis‐prone Junbo (C3H/HeH) mice promoted lower infection rates in the nasopharynx and middle ear, respectively. In conclusion, our results suggest that IgG directed against NTHi EF‐Tu may play an important role in the host immune response against NTHi.

Highlights

The Gram-negative bacterium Haemophilus influenzae is subdivided into encapsulated serotypes a–f that harbor a polysaccharide capsule, and the unencapsulated non-typeable H. influenzae (NTHi)
To assess whether IgG antibodies against elongation factor thermo unstable (EF-Tu) appears in young and adult humans upon natural exposure to respiratory pathogens, sets of different age-matched sera were collected from preschool children and healthy adult blood donors
Here. we show that IgG Abs directed against EF-Tu are present in children, and that titers increase in an age-dependent manner

Summary

Introduction

The Gram-negative bacterium Haemophilus influenzae is subdivided into encapsulated serotypes a–f that harbor a polysaccharide capsule, and the unencapsulated non-typeable H. influenzae (NTHi). Since the introduction of a capsule-based vaccine against H. influenzae type b (Hib) in the 1990s, NTHi has become the most common H. influenzae causing human disease. NTHi often resides asymptomatically in preschool children, and mainly causes opportunistic upper respiratory tract infections, including sinusitis and acute otitis media (AOM) [1]. Patients suffering from chronic obstructive pulmonary disease (COPD) are frequently colonized with NTHi, leading to exacerbations and increased morbidity [2]. NTHi can cause invasive disease, but is mainly isolated in immuncompromised hosts or patients with comorbidities [3]. A vaccine against NTHi is sought for in order to prevent disease of individuals at risk, and in recent years several vaccine antigens have been defined [5]

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Conclusion