Abstract
ABSTRACTIn modern-day vaccine design, a good pneumococcal capsular polysaccharide vaccine is measured by its ability to induce opsonic antibodies. These antibodies label bacteria for phagocytosis by neutrophils and thereby overcome the capsule’s barrier function. Doyle and Pirofski have raised a serious challenge to the current paradigm by describing anti-capsular antibodies that are highly protective but nonopsonic [C.R. Doyle and L. Pirofski, mBio 7(1):e02260-15, 2016, doi:10.1128/mBio.02260-15]. In fact, some functions are not related to neutrophils or phagocytosis at all. An increased awareness of these activities is critical not only for accurate comparisons of vaccine candidates but also for improvements in vaccination outcomes in settings of neutropenia. When vaccine developers select a single gatekeeper assay (e.g., an opsonophagocytic assay for bacteria or a neutralization assay for viruses), promising vaccine candidates may be missed. Doyle and Pirofski stress that multiple functions, not just one, should be investigated to enhance discovery of antibody mechanisms and to best assess vaccine-induced correlates of immune protection.
Highlights
Streptococcus pneumoniae is a leading cause of pneumonia, sepsis, and meningitis and remains the most common agent leading to hospitalization in all age groups
Based on the current paradigm that OPKA associates with protection, it was predicted that 7A9 would be better than 1E2 at preventing nasopharyngeal (NP) colonization and bacterial dissemination to the lungs and blood of mice challenged intranasally with a serotype 3 strain of pneumococcus
The authors found that when antibodies were delivered passively by the intraperitoneal route, 1E2 significantly reduced NP colonization and prevented early dissemination to lungs and blood, whereas 7A9 did not reduce NP colonization and reduced levels of bacteria in the blood only after 6 days of infection
Summary
Doyle and Pirofski describe two mouse monoclonal pneumococcal capsular polysaccharide serotype 3 (PPS3)-specific IgG1 antibodies, 7A9 and 1E2. The authors found that when antibodies were delivered passively by the intraperitoneal route, 1E2 significantly reduced NP colonization and prevented early dissemination to lungs and blood, whereas 7A9 did not reduce NP colonization and reduced levels of bacteria in the blood only after 6 days of infection When delivered intranasally, both antibodies reduced NP CFU, but 7A9 was dependent on the presence of Fc, whereas 1E2 was not. 1E2 and 7A9 were tested in a lethal pneumonia model using a different serotype 3 strain, administered intranasally In that case, both antibodies afforded protection and 7A9 reduced lung and blood CFU better than did 1E2. The excellent outcomes mediated by just two monoclonal antibodies were not correlated with the gold-standard assay
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