Panel 8: Vaccines and immunology

Abstract

Objective: To review and highlight significant advances made towards vaccine development and understanding of the immunology of otitis media (OM) since the 19th International Symposium on Recent Advances in Otitis Media (ISOM) in 2015, as well as identify future research directions and knowledge gaps.

Data sources: PubMed database, National Library of Medicine.

Review methods: Key topics were assigned to each panel member for detailed review. Draft reviews were collated, circulated, and thoroughly discussed when the panel met at the 20th ISOM in June 2019. The final manuscript was prepared with input from all panel members.

Conclusions: Since 2015 there have been a number of studies assessing the impact of licensed pneumococcal vaccines on OM. While these studies have confirmed that these vaccines are effective in preventing carriage and/or disease caused by vaccine serotypes, OM caused by non-vaccine serotype pneumococci and other otopathogens remains a significant health care burden globally. Development of multi-species vaccines is challenging but essential to reducing the global burden of OM. Influenza vaccination has been shown to prevent acute OM, and with novel vaccines against nontypeable Haemophilus influenzae (NTHi), Moraxella catarrhalis and Respiratory Syncytial Virus (RSV) in clinical trials, the potential to significantly prevent OM is within reach. Research into alternative vaccine delivery strategies has demonstrated the power of maternal and mucosal vaccination for OM prevention. Future OM vaccine trials must include molecular diagnostics of middle ear effusion, for detection of viruses and bacteria that are persisting in biofilms and to enable accurate assessment of vaccine impact on OM etiology. Understanding population differences in natural and vaccine-induced immune responses to otopathogens is also important for development of the most effective OM vaccines. Improved understanding of the interaction between otopathogens will also advance development of effective therapies and encourage the assessment of the indirect benefits of vaccination.

Implications for practice: While NTHi and M. catarrhalis are the predominant otopathogens, funding opportunities to drive vaccine development for these species are limited due to a focus on prevention of childhood mortality rather than morbidity. Delivery of a comprehensive report on the high financial and social costs of OM, including the potential for OM vaccines to reduce antibiotic use and subsequent development of antimicrobial resistance (AMR), would likely assist in engaging stakeholders to recognize the value of prevention of OM and increase support for efforts on OM vaccine development. Vaccine trials with OM prevention as a clinical end-point are challenging, however a focus on developing assays that measure functional correlates of protection would facilitate OM vaccine development.

Keywords: Adaptive immunity; Clinical trial; Innate immun*; Otitis media AND; Vaccine.

Figure 1.

Etiologies of acute and “complicated” otitis media from studies from 2012 to present. Top: Etiology of AOM based on results of culture and polymerase chain reaction (PCR) analysis of middle ear fluids from 11 studies from 2012 to present [, –128]. Bottom: Etiology of “complicated” OM based on results of culture and PCR analysis of middle ear fluids from 9 studies from 2012 to present [–, , –129]. Complicated OM includes recurrent OM, treatment failure, chronic OM, and OM with effusion. Numbers at the bottom of the bars indicate the number of samples upon which results are based. Abbreviations: S.pn, Streptococcus pneumoniae; NTHi, non-typeable Haemophilus influenzae; Mcat, Moraxella catarrhalis.