Age-related immune response to pneumococcal polysaccharide vaccination: lessons for the clinic

Abstract

Due to distinct immunological limitations, both infants and elderly individuals are highly susceptible to Streptococcus pneumoniae. Routine immunization of children with the conjugate vaccine over the past decade has substantially reduced incidence of vaccine-serotype related invasive pneumococcal disease in both vaccinated and unvaccinated persons of all ages. However, disease burden remains high in the elderly despite the effects of herd protection and recommended use of polysaccharide vaccine in this population for over 30 years. An increase in drug resistance and incidence of infections caused by non-vaccine serotypes emphasize the need to improve current vaccination strategies. Recent efforts to identify age-associated defects in vaccine response and the use of conjugate vaccine and potential alternatives in adults are discussed.

Keywords:

• aging
• B cells
• children
• conjugate
• pneumococcal protein
• polysaccharide
• Streptococcus pneumoniae
• vaccine

Acknowledgements

The authors thank Dr. D Leggat and Dr. N Khaskhely for their contributions to this work.

Financial & competing interests disclosure

This work was supported by NIH R01AG015978 and R01A081558 grants to MA Julie Westerink. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Streptococcus pneumoniae remains a significant cause of morbidity and mortality worldwide. The clinical spectrum of disease ranges from localized infections, including otitis media, sinusitis and pneumonia, to invasive disease, including bacteremia and meningitis. Anti-capsular antibodies generated by B cells confer protection.

• Due to concerns regarding drug resistance and optimal therapeutic approaches, prophylactic measures are highly desirable. A purified pneumococcal polysaccharide vaccine and a conjugated vaccine are currently available for use.

• The ability to respond to polysaccharide antigens is age-dependent and does not develop until 2 years of age. In contrast, the ability to respond to protein antigens is present at birth. Use of the conjugate vaccine has improved immune responses to polysaccharides in young children.

• Elderly individuals exhibit decreased efficacy to polysaccharide vaccination compared with younger adults. Despite undiminished production of IgG antibody after vaccination, older adults exhibit decreased opsonic activity. Decreased antibody functionality in the elderly is attributed to reduced IgM production post-vaccination in addition to differences in antibody structure and repertoire diversity.

• Circulating splenic marginal zone, or IgM memory, B cells and B-1 cells are considered to be the primary B-cell subsets responsible for producing antibodies to polysaccharide antigens.

• B-cell populations important for immunity to polysaccharides are altered in young children. B-1 cell frequencies peak at infancy and decline with age. In contrast, circulating IgM memory B cells are nearly undetectable at birth but gradually increase with age as a result of splenic maturation processes that occur until 2 years of age.

• Phenotypic analysis of B-cell subsets that respond to pneumococcal vaccination revealed distinct differences between young and old adults. In younger adults, IgM memory B cells are the predominant B-cell population; in contrast, in elderly individuals, responding B cells are primarily switched memory B cells.

• Routine conjugate vaccination for over the past decade has substantially reduced invasive disease incidence and pneumonia-related hospitalizations in both vaccinated children and unvaccinated adults due to herd protection. High immunogenicity and efficacy of the conjugate vaccine in young children led to the consideration of routine use in older adults. Efficacy and surveillance studies are currently underway to determine whether vaccination policies should be changed.

• The phenomenon of serotype replacement has rekindled interest in development of novel pneumococcal vaccines. Multiple potential candidates for protein-based or whole cell vaccines have been identified in pre-clinical studies.

Notes