The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection
Section snippets
Polysaccharide vaccines
It was demonstrated over 60 years ago that vaccines could be used to protect humans from pneumococcal infection [1]. The pneumococcal vaccine in widespread use at the present contains 23 different capsular polysaccharides and is efficacious in adults [2], [3]. Unfortunately, this vaccine was not able to elicit protective antibodies in infants, one of the major target groups of immunization. It was also no more than 60% efficacious in protecting the elderly from pneumococcal infection [4]. More
Pneumococcal protein candidates for vaccines
Because of these problems, several pneumococcal proteins that have been shown to elicit protection in mice (PspA, pneumolysin, PsaA, PspC and others [6], [7], [8] have been proposed as vaccine candidates. Recent studies at UAB, done in collaboration with James Paton [9] and Eddie Ades [10], have provided data on the comparative utility of these proteins in vaccines. Many of these results are still unpublished, but a summary of the general results is provided (Fig. 2). These studies have also
PspA
One of these proteins, PspA has recently undergone phase one clinical trials in man and has been found to be safe and highly immunogenic [11]. PspA is a protein that is found on all pneumococci [12]. PspA is able to interfere with fixation of complement component C3, thus potentially blocking downstream events leading to opsonization and phagocyte chemotaxis [13].
PspA has three major structural domains. The N-terminal, about 40% of the molecule, has a sequence consistent with a coiled-coil
Elicitation of protective antibody to PspA in man
While these studies have been encouraging regarding the potential development of a PspA vaccine, direct evidence that human antibodies to PspA could be protective has been lacking. There is some indirect evidence, however, that human antibody to PspA can be protective. Virolainen et al. showed that among children with invasive infections, those with the lowest titers of antibody to PspA are the ones who are infected most frequently with pneumococci [22]. These studies are correlative, however,
Potential application of pneumococcal proteins to human vaccines
PspA could be used in several different ways in the formulation of human vaccines. One possibility would be to formulate a vaccine containing a few PspAs of each of the two PspA families. If sufficiently efficacious, PspA could permit the development of a stand alone protein vaccine that would be much less costly to produce than conjugate vaccines. Another possibility would be to include one or more other pneumococcal proteins in the vaccine to maximize protection. A highly effective vaccine
Acknowledgements
Our studies have been supported by NIH, Grants AI21548 and HL58418, and support from Aventis Pasteur, Swiftwater, PA. Contributions to these studies from collaborators, J. S. Sampson and E. W Ades, at the Centers for Disease Control in Atlanta, and J. C. Paton A. G. Ogunniyi. at the Woman’s and Children’s Hospital in Adelaide, Australia, are greatly appreciated.
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Cited by (122)
Rational selection of broadly cross-reactive family 2 PspA molecules for inclusion in chimeric pneumococcal vaccines
2017, Microbial PathogenesisCitation Excerpt :In order to improve the coverage of the existing polysaccharide-based vaccines, several conserved proteins have been investigated as alternative low cost strategies [3–6]. Pneumococcal Surface Protein A (PspA) is a largely studied virulence factor, able to induce protection in several animal models [7–12]. PspA is present in virtually all pneumococcal strains and is exposed at the bacterial surface, where it may interact with antibodies, complement molecules and other immune mediators [13].
Pneumococcal Conjugate Vaccine and Pneumococcal Common Protein Vaccines
2017, Plotkin's VaccinesVaccine Potential of Pneumococcal Proteins
2015, Streptococcus Pneumoniae: Molecular Mechanisms of Host-Pathogen InteractionsGenetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses
2015, VaccineCitation Excerpt :However, these experiments do not directly demonstrate that the enhanced proliferative responses induced at higher concentrations of the fusion protein are directed against PsaA. Previously we and others have shown that PsaA is a good T-cell antigen and pneumococcal vaccine candidate [23–25,36], but we did not detect any proliferative responses to PsaA alone in the concentration range 0.04–1.28 μg/ml at which most of the cell cultures were stimulated. To test our antigen delivery hypothesis further, higher concentrations (8 μg/ml) of PsaA were tested and enhanced responses, presumably by increasing antigen uptake by APCs, thus circumventing any requirement for enhanced antigen-delivery by Ply/Δ6Ply (data not shown).