Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Abstract

dStreptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccinetype pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

Evaluation of Pneumococcal Surface Protein A as a Vaccine Antigen against Secondary Streptococcus pneumoniae Challenge during Influenza A Infection

“…Several recent studies reported that PspA vaccination can induce a protective antibody response and enhance bacterial clearance during influenza-S. pneumoniae co-infection [21,32,33]. The distinctions between our studies and earlier works published by others are that (1) we compared our immunization to Prevnar13, the FDA approved anti-pneumococcal vaccine, and showed that PspA is equally as protective; (2) we showed that PspA can protect against more than one pneumococcal strain, specifically serotype 2 D39, which is a strain not included in Prevnar13; and (3) we showed that protection is dependent on the bacterial challenge dose.…”

Protective responses of an engineered PspA recombinant antigen against Streptococcus pneumoniae

“…The limited vaccine coverage, replacement by non-vaccine serotypes [3] and non-encapsulated S. pneumoniae (NESp) which have been isolated from patients with invasive and non-invasive pneumococcal disease [5,6] and increasing antibiotic resistance [7] are some serious threats in the near future; Therefore, the search for new candidates for a vaccine that elicit protection against a broader range of pneumococcal strains is necessary [[8], [9], [10]]. Pneumococcal surface protein A (PspA) is a very promising candidate for novel vaccine development against pneumococcal infections [11]. PspA have been found in all the clinical isolates [[12], [13], [14]].…”

Molecular characterization of Streptococcus pneumoniae, particularly serotype19A/ST320, which emerged in Krasnoyarsk, Russia

“…Mucosal/non‐invasive infections include non‐bacteremic pneumonia, AOM and sinusitis, which are less severe, but very common health issues . The most frequent S. pneumoniae infection is AOM, including patients in whom it is a complication of influenza .…”