A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae

Abstract

Infections caused by Streptococcus pneumoniae are a major cause of mortality throughout the world. Protein-based pneumococcal vaccines are envisaged to replace or complement the current polysaccharide-based vaccines. In this context, detoxified pneumolysin (dPly) and pneumococcal histidine triad protein D (PhtD) are two potential candidates for incorporation into pneumococcal vaccines. In this study, the protective efficacy of a PhtD-dPly vaccine was evaluated in a rhesus macaque (Macaca mulatta) model of pneumonia. The animals were immunized twice with 10 µg of PhD and 10 µg of dPly formulated in the Adjuvant System AS02 or with AS02 alone, before they were challenged with a 19F pneumococcal strain. The survival was significantly higher in the protein-vaccinated group and seemed to be linked to the capacity to greatly reduce bacterial load within the first week post-challenge. Vaccination elicited high concentrations of anti-PhtD and anti-Ply antibodies and a link was found between survival and antibody levels. In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies.

Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

“…Godfroid et al also showed a role for anti-PhtD human antibody in protection against lethal intranasal challenge in a mouse model (49); however, they did not use Fabs. Vaccination of rhesus macaques with PhtD has been shown to elicit protection against pneumonia (50) and is currently in human clinical trials (51). To our surprise, antibodies specific to Ply, which do not have a role in blocking adherence of S. pneumoniae to human lung epithelial cells, showed the greatest level of protection against NP colonization in mice.…”

Neutralizing Antibodies Elicited by a Novel Detoxified Pneumolysin Derivative, PlyD1, Provide Protection against Both Pneumococcal Infection and Lung Injury

“…Due to the lytic activity of PLY, several reducedtoxicity derivatives have been evaluated preclinically for their immunogenicity and protective capacity. Vaccination with some of these PLY derivatives has been shown to delay the onset of disease (1,8,18,27), albeit via an uncertain mechanism(s). In some cases these PLY derivatives such as PdB still retained residual hemolytic activity (9).…”

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

“…Several PFTs have been shown to be immunogenic, such as S. pneumoniae PLY, S. aureus alpha-toxin, M. tuberculosis ESAT-6, and L. monocytogenes LLO (370)(371)(372)(373), but detailed studies on specific effects of PFTs on the adaptive immune system are scarce.…”

“…PFTs may be viable targets for vaccination against bacterial infection, as observed, for instance, for S. pneumoniae, S. aureus, M. tuberculosis, and L. monocytogenes (370)(371)(372)(373). Although active immunization against ALO protected mice from purified ALO, it did not protect them from B. anthracis infection (474).…”