Pneumococcal whole-cell and protein-based vaccines: changing the paradigm

Abstract

Introduction. Epidemiologic evaluations of Streptococcus pneumoniae nasopharyngeal (NP) colonization and pneumococcal disease suggest that newer serotypes in future formulations of pneumococcal conjugate vaccines (PCVs) are needed and there may need to be continued reformulations because there are many new emerging serotypes expressed by pneumococci. Areas Covered: Mechanisms of protection by next-generation whole-cell vaccine (WCV) and/or multi-component pneumococcal purified protein vaccines (PPVs) in development for prevention of pneumococcal infections. Expert Commentary: A long-term strategy for prevention of pneumococcal disease will likely include WCV and PPVs. However these vaccines will impact disease pathogenesis in a different manner than PCVs. Prevention of pneumococcal NP colonization should not be expected, nor is it desirable because risks for NP colonization by other replacement organisms into the ecological niche vacated by all pneumococci may have consequences. The expression biology of capsule and surface protein antigens are phase dependent. Therefore, the immune response will be different and the mechanism of protection divergent. WCVs and PPVs may be alternative strategies in low income developing countries to protect against invasive disease and reduce NP carriage load.

Neutrophils are required during immunization with the pneumococcal conjugate vaccine for protective antibody responses and host defense against infection

“…In summary, we demonstrate here that PMNs are required at the time of immunization with the pneumococcal conjugate vaccine for optimal protective Ab responses and host protection against subsequent S. pneumoniae infection. As serotype replacement by bacterial strains not covered by the current vaccines continue to emerge, novel serotype-independent vaccine formulations such as whole cell vaccines or common pneumococcal protein vaccines are being considered [48]. Therefore, future vaccine designs should take PMN responses into consideration, particularly in susceptible populations like the elderly [2], where PMN responses are known to be dysregulated [49].…”

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children

“…The concept of a disassociation between antibody levels that protect against infection but do not prevent NP colonization is new [21]. Up to now, it was presumed that protection from Spn infections by pneumococcal protein vaccines would be the same as PCVs, demonstrating a strong correlation with induction of high serum and mucosal antibodies that provide protection from acquisition of NP colonization and infection.…”

“…To date, there are 97 distinct serotypes according to capsular polysaccharide composition [29]. Within a few years of introduction of each of the PCVs, emergence of non-vaccine replacement serotypes has been noted in numerous studies [29, 10, 21]. Therefore, we and others have been evaluating next-generation purified pneumococcal protein vaccines that will be composed of highly conserved proteins expressed by virtually all Spn [10, 21].…”

“…Within a few years of introduction of each of the PCVs, emergence of non-vaccine replacement serotypes has been noted in numerous studies [29, 10, 21]. Therefore, we and others have been evaluating next-generation purified pneumococcal protein vaccines that will be composed of highly conserved proteins expressed by virtually all Spn [10, 21]. We have studied three pneumococcal proteins: histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply) and have shown that natural exposure to Spn following nasopharyngeal (NP) colonization elicits both serum and mucosal antibody responses in young children [22, 31].…”

Paediatric and adult bronchiectasis: Vaccination in prevention and management

“…Importantly, new vaccines need to be cheap, cost‐effective and readily administered, particularly given the burden of disease is often highest in low‐income countries. Ideally, they should provide herd protection, although preliminary results do not look promising and new vaccine scheduling strategies may be required . Moreover, these vaccines remain a distance from licensure and potentially even further from evaluation in patients with bronchiectasis.…”