Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens

Abstract

Naturally acquired immunity against invasive pneumococcal disease (IPD) is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG), representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule.

Streptococcus pneumoniae Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies

“…The fact that natural protection against pneumococcal colonization is dependent on antibodies to pneumococcal proteins, rather than capsular polysaccharide, suggests that an approach involving protein vaccine candidates may be most fruitful [109]. Whole-cell vaccines and protein vaccines with broad coverage across the over 95 serotypes are two approaches that have been suggested and investigated [94, 107••].…”

Integrative Physiology of Pneumonia

“…of protein epitopes from pneumococcus (157), and raising antibodies against some of these pneumococcal antigens by vaccinating mice can improve defense against pneumococcal pneumonia (157,334), by mechanisms including opsonophagocytosis, decreased adherence, disruption of toxins, and more. Human blood from any of at least three different continents consistently contains IgG antibodies against a common set of diverse pneumococcal proteins, and delivering human IgG (without antigen selection) to mice is sufficient to diminish the severity of infection during pneumococcal pneumonia (538). However, pneumococcus-recognizing antibodies found in the blood after pneumococcal infection are not necessarily capable of mediating heterotypic protection (84,157).…”

“…High levels of secondhand smoke or of air pollution also associate with increased risk for and severity of pneumonia (7,364,538). These exposures contain similar particulate matter and toxic compounds like acrolein, so pneumonia susceptibility due to secondhand smoke and air pollution may be from overlapping mechanisms with tobacco smoking.…”

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

“…[24 ] However, naturally acquired protection against IPD depends on antibody to protein antigens rather than capsule as shown in a murine model using human antibodies. [25]While there is a significant difference in quantitative expression of capsule between variants [26], it is unclear as to differences in expression of membrane proteins between variants of the same strain. [27–29]…”

“…[24 ] However, naturally acquired protection against IPD depends on antibody to protein antigens rather than capsule as shown in a murine model using human antibodies. [25]…”