Question

Name: 18. The current vaccine for S. pneumoniae is made up of 23 different capsular polysaccharides. How would you propose to make a protein-targeted vaccine that is protective to all S. pneumoniae serotypes? Hint: you first need to figure out what proteins are recognized by immune people. Include the key technique for determining this. (6 points)

Answer 1

ANSWER

All currently available Spn vaccines have limitations due to their capsular serotype composition . Both PPV and PCVs are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines.For instance, after introduction of PCV-7, IPD and acute otitis media (AOM) cases caused by serotype 19A dramatically increased, including emergence of a strain that was resistant to all antibiotics approved for children.9,15,16 Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and AOM than against IPD.3,17 There has been only a marginal decline in overall AOM rate in child populations since introduction of PCV13. However serotype specific reductions in AOM caused by Spn strains expressing the 6 new serotypes included in PCV13 have not been demonstrated. Such a study is ongoing with results expected in 2016 . These shortcomings of capsular polysaccharide-based Spn vaccines has created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections.3Therefore, research scientists from academia and industry have been seeking Spn protein vaccine candidates that are universally expressed by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines.

Spn is a commensal of the nasopharynx (NP) and only becomes pathogenic when changes in the NP, typically caused by viral upper respiratory infections, allow the organism to achieve a pathogenic inoculum that overcomes innate and adaptive host defense.2Spn carriage is most prevalent in vulnerable populations such as young children, immunocompromised adults, and the elderly.In children under 5 years of age, Spn can be detected in the NP from 10% up to 90% of children with the variation mostly attributable to the frequency of NP sampling, and study population.The burden of non-invasive and invasive Spn disease correlates with the NP carriage rate. Children in developing countries generally have a higher carriage rate and density of organisms than in developed countries. Spn colonization is an immunizing event that leads to the generation of antigen specific antibodies and cellular immunity, and is therefore beneficial for the host. However, colonization is also a prerequisite for Spn diseases.24 The strategy currently guiding vaccination with polysaccharide-based conjugate vaccines seeks to prevent Spn disease by completely eliminating colonization.34–36 This has been an overwhelming success with respect to the Spn serotypes included in the vaccines.

Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. Therefore, the challenge before vaccinologists is to define the NP carriage threshold below which perturbations by viral co-infections will not enable Spn to make the transition to invasive pathogen.