PHiD-CV induces anti-Protein D antibodies but does not augment pulmonary clearance of nontypeable Haemophilus influenzae in mice. Issue 38 (11th September 2015)

• Record Type: Journal Article
• Authors: Siggins, Matthew K.; Gill, Simren K.; Langford, Paul R.; Li, Yanwen; Ladhani, Shamez N.; Tregoning, John S.
• Is Part Of: Vaccine. Volume 33:Issue 38(2015)
• Page Start: 4954
• Page End: 4961
• Publication Date: 2015-09-11
• Subjects: Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.07.034
• Languages: English
• ISSNs: 0264-410X

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">A recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD-CV; Synflorix, GSK) uses Protein D from <italic>Haemophilus influenzae</italic> as a carrier protein. PHiD-CV therefore has the potential to provide additional protection against nontypeable <italic>H. influenzae</italic> (NTHi). NTHi frequently causes respiratory tract infections and is associated with significant morbidity and mortality worldwide and there is currently no vaccine.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">We developed mouse models of NTHi infection and influenza/NTHi superinfection. Mice were immunized with PHiD-CV, heat-killed NTHi, or a 13-valent pneumococcal conjugate vaccine that did not contain Protein D (PCV13; Prevenar, Pfizer) and then infected intranasally with NTHi.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">Infection with NTHi resulted in weight loss, inflammation and airway neutrophilia. In a superinfection model, prior infection with pandemic H1N1 influenza virus (strain A/England/195/2009) augmented NTHi infection severity, even with a lower bacterial challenge dose. Immunization with PHiD-CV produced high levels of antibodies that were specific against Protein D, but not heat-killed NTHi. Immunization with PHiD-CV led to a slight reduction in bacterial load, but no change in disease outcome.</p> </sec> <sec> <title id="sect0025">Conclusions</title> <p id="spar0020">PHiD-CV induced high levels of Protein D-specific antibodies, but did not augment pulmonary clearance of NTHi. We found no evidence to suggest that PHiD-CV will offer added benefit by preventing NTHi lung infection.</p> </sec> </abstract>