Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates

Abstract

Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes (up to 100 different serotypes have been identified) and are unable to protect against non-vaccine serotypes and non-encapsulated pneumococci. The emergence of antibiotic-resistant non-vaccine serotypes after these vaccines is an increasing threat. Therefore, there is an urgent need to develop new pneumococcal vaccines which could cover a wide range of serotypes. One of the vaccines most characterized as a prophylactic alternative to current PPV-23 or PCVs is a vaccine based on pneumococcal protein antigens. The choline-binding proteins (CBP) are found in all pneumococcal strains, giving them the characteristic to be potential vaccine candidates as they may protect against different serotypes. In this review, we have focused the attention on different CBPs as vaccine candidates because they are involved in the pathogenesis process, confirming their immunogenicity and protection against pneumococcal infection. The review summarizes the major contribution of these proteins to virulence and reinforces the fact that antibodies elicited against many of them may block or interfere with their role in the infection process.

Pneumococcal Surface Proteins as Virulence Factors, Immunogens, and Conserved Vaccine Targets

“…CBPs are especially interesting because many orthogonal approaches have unbiasedly reached the same conclusion: most CBPs contribute to bacterial virulence, and are immunogenic targets in human sera exposed to pneumococcal pneumonia ( Giefing et al., 2008 ). Recent advances have been made toward CBPs as candidate antigens in vaccine design as well as expanded knowledge on pathogenicity and virulence mechanisms ( Sempere et al., 2021 ). Here, we review CBPs that have shown contributions to Spn pathogenicity and are utilized in preclinical vaccine studies and clinical trial vaccine formulations.…”

A Jack of All Trades: The Role of Pneumococcal Surface Protein A in the Pathogenesis of Streptococcus pneumoniae

“…This concern overlaps the mosaic nature of PspA with regard to its ability to evade the host immune response and indicates that to avoid "PspA replacement" or emergence of a non-typable PspA version, any multi-valent PspA vaccine should be developed that covers conserved regions under both positive and negative pressure by the host (Yamaguchi et al, 2019). The risk of this can also be diminished by including more than one protein in any vaccine formulation, such as pneumolysin (Sempere et al, 2021).…”

“…The major concerns regarding the use of PspA in a pneumococcal vaccine stem from the lack of cross-reactivity between all the clades. Antibody against clades 1 and 2 are cross protective, however, cross protection is reduced with consideration to clades 3, 4, and 5 ( Sempere et al., 2021 ). This concern overlaps the mosaic nature of PspA with regard to its ability to evade the host immune response and indicates that to avoid “PspA replacement” or emergence of a non-typable PspA version, any multi-valent PspA vaccine should be developed that covers conserved regions under both positive and negative pressure by the host ( Yamaguchi et al., 2019 ).…”

“…This concern overlaps the mosaic nature of PspA with regard to its ability to evade the host immune response and indicates that to avoid “PspA replacement” or emergence of a non-typable PspA version, any multi-valent PspA vaccine should be developed that covers conserved regions under both positive and negative pressure by the host ( Yamaguchi et al., 2019 ). The risk of this can also be diminished by including more than one protein in any vaccine formulation, such as pneumolysin ( Sempere et al., 2021 ). Another concern was raised when it was found that PspA has low sequence homology with human cardiac myosin, which may elicit the production of autoantibodies against cardiac tissue leading to inflammation and tissue damage along with autoimmune disease ( Ginsburg et al., 2012 ).…”

If Not Now, When? Nonserotype Pneumococcal Protein Vaccines

“…There has long been interest in and growing support for developing such a vaccine based on pneumococcal proteins. Pneumococcal proteins with vaccine potential have been extensively studied [ 13 ] and proposed as vaccine candidates based on their distribution among all capsule types and their ability to elicit protective immune responses against systemic infection in animal models. Such a vaccine would likely be immunogenic in young children, be less expensive to produce, and elicit strong immunological memory at least of the magnitude seen with conjugated CP.…”