Diana C. Otczyk

Prospects for a vaccine against otitis media

Otitis media is a major cause of morbidity in 80% of all children less than 3 years of age and often goes undiagnosed in the general population. There is evidence to suggest that the incidence of otitis media is increasing. The major cause of otitis media is infection of the middle ear with microbes from the nasopharynx. The anatomical orientation of the eustachian tube, in association with a number of risk factors, predisposes infants and young children to the infection. Bacteria are responsible for approximately 70% of cases of acute otitis media, with Streptococcus pneumoniae, nontypeable Haemophilus influenzae and Moraxella catarrhalis predominating as the causative agents. The respiratory viruses, respiratory syncytial virus, rhinovirus, parainfluenza and influenza, account for 30% of acute otitis media cases. Over the past decade, there has been a profound increase in the reported resistance to antibiotics, which, with increased disease burden, has focussed attention on vaccine development for otitis media. A polymicrobial formulation containing antigens from all major pathogens would have the greatest potential to deliver a sustained reduction in the disease burden globally. The disappointing outcomes for otitis media seen with the polysaccharide pneumococcal conjugate vaccine have raised major challenges for the vaccination strategy. Clearly, more knowledge is required concerning immune mechanisms in the middle ear, as well as vaccine formulations containing antigens that are more representative of the polymicrobial nature of the disease. Antigens that have been extensively tested in animal models are now available for testing in human subjects.

Mucosal immunization: a realistic alternative.

Most infections occur at or through mucosal surfaces. Despite this knowledge, current vaccination practices rely predominantly on parenteral administration with only a few vaccines being registered for administion by the mucosal route. Whilst mucosal immunization brings many advantages, the lack of reliable delivery systems has been a major drawback to date. With the recent advances in delivery system technology and the improved understanding of site specific mucosal immune mechanisms, mucosal immunization offers an exciting alternative vaccination strategy.

Developmental Profiles of Mucosal Immunity in Pre-school Children

This study investigated the effect of attending pre-school on mucosal immunity. Children 3.5 to 5 years of age who attended pre-school were observed for a 10 month period. Demographic information was collected on previous childcare experiences, the home environment and clinical information relating to the child and the family. A daily illness log was kept for each child. A multivariate longitudinal analysis of the relation between immunoglobulins in saliva and age, gender, childcare experience, pre-school exposure, number of siblings, environmental tobacco smoke (ETS), atopy and hospitalisation was conducted. There was a positive association of higher IgA levels with the winter season and with children being older than 4 years (P < .001), having attended childcare prior to commencing pre-school (P < .05), and having been exposed to ETS at home (P < .05). Lower IgA levels were associated with being atopic (P < .05). Higher IgG levels were associated with exposure to ETS (P < .001), while lower levels were associated to having atopy. Higher IgM levels were associated with previous childcare experience (P < .01) whilst having been hospitalised was associated with having low salivary IgM levels (P < .01). Lagged analyses demonstrated that immunological parameters were affected by the number of respiratory infections in the preceding 2 months.

Vaccination for the control of childhood bacterial pneumonia - Haemophilus influenzae type b and pneumococcal vaccines

Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia. The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children. However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement. The current vaccines provide serotype-specific, antibody-mediated protection against only a few of the 90+ capsule serotypes. Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries. The next generation of pneumococcal vaccines have advanced to clinical trials.

Haemophilus influenzae and smoking-related obstructive airways disease

Background Intralumenal bacteria play a critical role in the pathogenesis of acute infective episodes and airway inflammation. Antigens from colonizing bacteria such as nontypeable Haemophilus influenzae (NTHi) may contribute to chronic lung disease through an immediate hypersensitivity response. The objective of this study was to determine the presence of specific NTHi-IgE antibodies in subjects with chronic bronchitis (CB) and COPD who had smoked. Methods Serum, sputum, and saliva samples were collected from subjects with CB and moderate–severe COPD and healthy aged-matched controls. Total IgE and specific NTHi IgE were measured by enzyme linked immmunosorbent assay. Throat swabs were examined for the presence of NTHi. Results The results demonstrate that: i) specific NTHi IgE antibodies occur at a low level in healthy subjects; ii) those with both CB and moderate–severe COPD have elevated specific NTHi IgE antibody compared with healthy controls, with higher levels in those with most severe disease; iii) IgE levels are greater in those with moderate–severe COPD than in those with CB. They demonstrate specific NTHi IgE antibody is regularly found at higher than normal levels in COPD. Conclusion The detection of IgE antibody to colonizing bacteria in all subjects with CB or moderate–severe COPD identifies a possible mechanism of bronchospasm in these subjects amenable to specific intervention therapy.

Mucosal and systemic antibody responses to potential Pseudomonas aeruginosa vaccine protein antigens in young children with cystic fibrosis following colonization and infection

Pseudomonas aeruginosa is an important prognostic determinant in cystic fibrosis (CF). Little is known however, about P. aeruginosa induced local mucosal and systemic immune responses. Twenty CF children were categorized according to their P. aeruginosa status: (1) chronic lower respiratory tract infection (LRTI), (2) prior successfully treated initial LRTI, (3) isolated upper respiratory tract (URT) colonization, and (4) no known URT colonization or previous LRTI. Their antibody responses, and those of six non-CF disease controls, in serum and bronchoalveolar lavage (BAL) fluid to potential P. aeruginosa vaccine antigens outer membrane protein F (OprF), outer membrane protein H (OprH), catalase A (KatA) and a whole killed cell (WKC) extract were evaluated. Outer membrane protein G (OprG) responses were also measured in blood. Natural exposure, colonization and infection resulted in detectable antibody levels in BAL and serum in all CF groups. Both chronically infected and URT colonized CF children had substantially elevated immunoglobulin A antibody levels in the BAL fluid and sera toward the WKC extract and OprF antigen compared with the other groups of CF children and non-CF controls. The serum levels of specific P. aeruginosa antibodies involving immunoglobulin G and M isotypes increased with chronic LRTI, especially antibody levels to KatA, OprH and WKC extract, which were substantially greater in chronically infected children compared with all other groups. In conclusion, natural exposure, URT colonization and LRTI with P. aeruginosa all induce substantial mucosal and systemic antibody responses to potential vaccine antigens with chronically infected CF children having the highest levels.

Delivering vaccines for the prevention of pneumonia - programmatic and financial issues

Pneumonia is the leading cause of morbidity and mortality in children younger than 5 years. Vaccines are available against the main bacterial pathogens Haemophilus influenzae type b and Streptococcus pneumoniae. There are also vaccines against measles and pertussis; diseases that can predispose a child to pneumonia. Partners such as the Global Alliance for Vaccines and Immunisation (GAVI), the Hib Initiative, the Accelerated Development and Introduction Plan for pneumococcal vaccines and the Measles Initiative, have accelerated the introduction of vaccines into developing countries. Whilst significant improvements in vaccine coverage have occurred globally over the past decade, there still remains an urgent need to scale-up key pneumonia protection and treatment interventions as identified in the Global Action Plan for the Prevention and Control of Pneumonia (GAPP). There is promise that global immunisation will continue to improve child survival. However, there are several challenges to vaccine implementation that must first be addressed, including: a lack of access to under-served and marginalised populations; inadequate planning and management; a lack of political commitment; weak monitoring and surveillance programmes and assured sustainable finance and supply of quality vaccines. There is an urgent need to increase global awareness of the devastation that pneumonia brings to the worlds poorest communities.