Development of a Vaccine against Invasive Pneumococcal Disease Based on Combinations of Virulence Proteins of Streptococcus pneumoniae

Abstract

Current global efforts are focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. One such strategy involves the use of one or more pneumococcal protein antigens common to all serotypes, to provide cheap, non-serotype-dependent protection. In this study, we evaluated the protective efficacy of immunization of mice with PdB (a pneumolysin toxoid), PspA, PspC (CbpA), PhtB, and PhtE in an invasive-disease model. The antigens were administered in alum adjuvant, either alone or in various combinations. Protection against intraperitoneal challenge with virulent type 2 and 6A strains was assessed in two murine strains. Our findings show that in some situations, different individual proteins gave the best (and worst) protection. However, in many cases, a synergistic/additive effect was seen by using multiple proteins even where the individual proteins showed little value by themselves. For instance, the median survival times for mice immunized with combinations of PdB and PspA, PdB and PspC, or PspA and PspC were significantly longer than those for mice immunized with any of the single antigens. To date, the combination of PdB, PspA, and PspC offers the best protection.

Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

“…There is evidence that immunization with certain combinations of virulence proteins provides additive or even synergistic protection (5,25). The combination of Ply, PspA, and CbpA provided protection in mouse models especially successfully (7,11,26). These murine studies demonstrated a protective effect of immunoglobulins directed against these primarily but not exclusively surfacelocated pneumococcal proteins.…”

“…Most promise is offered by the addition of protein-based vaccines to the current PCV, which may provide protection regardless of serotype (3). Several protein antigens, such as Ply, CbpA, PspA, PsaA, PiaA, PhtB, PhtE (BVH-3), and NanA, have been identified as vaccine candidates (1,6,8,12,14,18,22,23,26,27,29,35). There is evidence that immunization with certain combinations of virulence proteins provides additive or even synergistic protection (5,25).…”

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

“…Among the different types of pneumococcal proteins such as pneumococcal surface protein A (PspA), pneumococcal surface protein C (PspC), pneumolysin; PspA is one of the most promising candidates and has been widely investigated by several groups (Briles et al, 2000a;Briles et al, 2000b;Haughney et al, 2013;Moreno et al, 2010;Ogunniyi et al, 2007;Ogunniyi et al, 2001;Vadesilho et al, 2012). The main function of PspA is preventing the deposition of complement on the surface of the bacterium thereby inhibiting opsonization and phagocytosis (Ren et al, 2004a;Ren et al, 2004b).…”

A Combination of Flt3 Ligand cDNA and CpG Oligodeoxynucleotide as Nasal Adjuvant Elicits Protective Secretory-IgA Immunity to Streptococcus pneumoniae in Aged Mice

“…Because pneumococcal infection is a major upper respiratory tract (URT) disease, which occurs on mucosal surfaces, one should take into account a mucosal vaccine strategy for developing an effective vaccine that could induce pathogen-specific immunity in the URT. Indeed, it has been shown that nasal immunization with pneumococcal surface protein A (PspA)-based vaccines in mice provided effective protective immunity against pneumococcal colonization and invasive infection (10)(11)(12)(13).…”