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A5485 - The Semi-Synthetic Streptococcus Pneumoniae Serotype 3 Tetrasaccharide Conjugate Protected Mice from Severe Pneumonia
Author Block: K. Reppe1, K. Hofmann1, S. Parameswarappa2, C. Pereira2, G. Nouailles1, A. von Bonin2, R. Klopfleisch3, P. Seeberger4, M. Witzenrath1; 1Department of Infectious and Respiratory Diseases, Charite - Universitätsmedizin Berlin, Berlin, Germany, 2Vaxxilon AG, Reinach, Switzerland, 3Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany, 4Max Planck Institute of Colloids and Interfaces, Potsdam and, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Rationale: Vaccination is the most important prophylactic strategy used worldwide to prevent invasive pneumococcal diseases. However, existing polysaccharide vaccines comprise only a part of the clinically relevant pneumococcal serotypes. Moreover, the ST3 glycoconjugates contained in the clinically used anti-pneumococcal vaccine Prevnar13® are less efficient and lead to hyporesponsiveness. A recently established chemical method now enables the rapid synthesis of structurally defined oligosaccharide antigens of Streptococcus pneumoniae. Thus, in the current study the protective effect of a new monovalent anti-ST3 glycoconjugate vaccine consisting of a synthetic capsular tetrasaccharide of S. pneumoniae serotype 3 was examined.
Methods: Female C57BL/6N mice were subcutaneously immunised with the monovalent glycoconjugate in combination with the adjuvant aluminium hydroxide (alum). Mice were boosted twice at three weeks intervals prior to transnasal infection with S. pneumoniae serotype 3. Further, additional experimental groups vaccinated with Prevnar13® or only adjuvant were used as positive and negative control, respectively.
Results: Vaccination with the anti-ST3 glycoconjugate or Prevnar13® activated adaptive immunity in mice and induced the production of specific antibodies. Vaccinated mice of both groups showed only mild clinical symptoms after infection with S. pneumoniae compared to non-vaccinated infected controls. Bacterial loads of lung tissue and blood were significantly decreased in mice vaccinated with anti-ST3 or Prevnar13®. Furthermore, immunisation with anti-ST3 or Prevnar13® significantly reduced the level of systemic leukocytopenia without compromising leukocyte recruitment into the lung.
Conclusions: The immunisation with the semi-synthetic monovalent anti-ST3 glycoconjugate in combination with alum improved pulmonary bacterial elimination and protected mice from severe pneumococcal pneumonia by inducing protective antibodies.
Funding: This work was supported by the German Research Foundation (SFB-TR 84, C3, C6 and C8) and Vaxxilon AG.