Serum Concentrations of Antibodies against Outer Membrane Protein P6, Protein D, and T- and B-Cell Combined Antigenic Epitopes of Nontypeable Haemophilus influenzae in Children and Adults of Different Ages

Abstract

e Nontypeable Haemophilus influenzae (NTHi) is one of the most common etiologies of acute otitis media, rhinosinusitis, and pneumonia. Outer membrane proteins (OMPs) are the main focus in new vaccine development against NTHi, as the H. influenzae type b (Hib) vaccine does not cover noncapsulated NTHi. The OMPs P6 and protein D are the most promising candidate antigens for an NTHi vaccine, and low antibody levels against them in serum may be correlated with infection caused by NTHi. In the current study, we measured the antibody titers against P6, protein D, and their T-and B-cell combined peptide epitopes in healthy individuals of different ages. We found that children <1 month old had the lowest antibody levels against NTHi P6, protein D, and their T-and B-cell combined antigenic epitopes. Antibody titers increased at ages 1 to 6 months, peaked at 7 months to 3 years, and remained high at 4 to 6 years. The antibody titers started to decrease after 6 years and were the lowest in the 21-to 30-year group. The geometric mean titers (GMTs) of T-and B-cell combined antigenic epitopes in P6 and protein D were positively correlated with those of the protein antigens. Among 12 peptides tested, P6-61, P6-123, and protein D-167 epitopes were better recognized than others in human serum. These findings might contribute to the development of an effective serotypeindependent vaccine for H. influenzae. Haemophilus influenzae is one of the normal inhabitants of the human nasopharynx and is responsible for pneumonia, acute otitis media (AOM), and acute rhinosinusitis (1-3). The presence or absence of a polysaccharide capsule segregates this bacterial species into two well-defined groups: one group of encapsulated strains and another group of noncapsulated strains, commonly referred to as nontypeable H. influenzae (NTHi) (3). Common infections caused by NTHi include otitis media in children and lower airway infections of chronic obstructive pulmonary disease in adults (4, 5). Vaccines composed of polysaccharide capsule conjugated to protein carriers have virtually eliminated infections caused by encapsulated H. influenzae type b, including meningitis and other systemic infections, in regions where the vaccines are widely administered (6, 7). However, these conjugate vaccines have no effect on infections caused by NTHi, and in regions with H. influenzae type b vaccination programs, nontypeable strains are now the most common cause of noninvasive H. influenzae infection, so that the development of the vaccine against NTHi is an urgent and challenging task (8-10).Since NTHi organisms are noncapsulated bacteria, the outer membrane proteins (OMPs) are the main targets for vaccine designers. Several research groups have identified conserved surface proteins and tested them as putative vaccines, and the conserved NTHi antigens with demonstrated preclinical protective capacity have been identified, among which P6 and protein D are the most widely studied (11)(12)(13)(14).Experimental data derived from humans and animal models indicate t...

Antibiotic Resistance Profiles of Haemophilus influenzae Isolates from Children in 2016: A Multicenter Study in China

“…An additional 11.1% of the HI strains isolated here were obtained from vaginal swabs of children with symptomatic vaginitis, suggesting that HI is also a common cause of vulvovaginal infection in prepubescent girls [13]. Infants, especially those less than 6 months old, have very low levels of HI antibodies in their blood [14] and are therefore highly susceptible to HI infection [3, 6, 13]. Infants infected with HI commonly develop pneumonia [13].…”

Patients with Chronic Obstructive Pulmonary Disease harbour a variation of Haemophilus species

“…Surface exposed proteins resulting from some of the genes discussed in this study, Protein D, Omp2 and Omp6, have also been investigated as potential vaccine candidates 52 – 54 . The importance for vaccination for NTHi does not come from its ability to cause invasive disease but is driven by the larger morbidity caused by NTHi in cases of otitis media and the role NTHi plays in triggering exacerbations in COPD.…”

Australian Aboriginal Children with Otitis Media Have Reduced Antibody Titers to Specific Nontypeable Haemophilus influenzae Vaccine Antigens

“…A recent study assessed the ontogeny of antibody responses to P6 and PD in children from birth to 6 years of age (47). The data indicated that children below the age of 1 month had the lowest antibody titers against P6 and PD; titers increased at 1 to 6 months, peaked at 7 months to 3 years, and then remained high at 4 to 6 years (47).…”

“…The data indicated that children below the age of 1 month had the lowest antibody titers against P6 and PD; titers increased at 1 to 6 months, peaked at 7 months to 3 years, and then remained high at 4 to 6 years (47). Interestingly, in our study of children between 1 and 15 years of age, while an increase in PD IgG antibody titers with age was observed for healthy control children (Table 2), no increase was observed for P6 (or P4).…”