For the prevention of invasive pneumococcal diseases, two polysaccharide vaccines are currently available: a non-conjugate vaccine, Pneumovax® (PPS23), and a conjugate vaccine, Prevenar13® (PCV13), inducing protection against 23 and 13 pneumococcal serotypes, respectively. The PPS23 is considered weakly immunogenic, especially in infants, elderly and immunocompromised patients, while PCV13 is now available for adults. In France, in April 2017, the new recommendations for at risk patients including asplenic patients are to revaccinate by PPS23 at least five years after the previous PPS23. However a phenomenon of vaccine hyporesponsiveness and a risk of immune tolerance to pneumococcus after repeated administrations of PPS23 are described. Large doses of polysaccharide antigens recruit memory and naive B cells, resulting in the production of low and high avidity antibodies, while low doses only stimulate memory B cells, inducing high affinity antibodies. Because of that, Swiss current recommendations are to revaccinate with PCV13 at 5 years the splenectomised patients. The recommendations of revaccination by PPS23 for USA or PCV13 for Switzerland have never been evaluated in clinical trial. Moreover, using combined PCV13/PPS23 could increase serotype coverage. Studying the immune response following combined revaccination by a boost dose of PCV13 following by PPS23 versus PPS23 alone will help to document and improve the vaccine recommendations.~The main objective is to evaluate at M13 the immunological response of 2 pneumococcal revaccination strategies (combined revaccination by a boost dose of PCV13 following 12 months later by PPS23, versus PPS23 alone), in splenectomised adults.~The primary endpoint is the proportion of patients responding to a minimum of 5 of the 9 serotypes analysed (9 serotypes among the 12 common serotypes to both PPS23 and PCV13: 1, 3, 6B, 7F, 9V, 14, 19A, 19F, and 23F) at M13 in each arm. A responder to a serotype is defined as a four-fold increase of the rate of OPA (OpsonoPhagocytic Assay) compared to baseline and titer ≥ LLOQ (Lower Limit of Quantification).
This research is a multi-center French randomized and double blind phase IIb clinical trial evaluating 2 revaccination strategies against pneumococcal infections among splenectomised patients. The main objective is to evaluate at M13 the immunological response of 2 pneumococcal revaccination strategies (combined revaccination by a boost dose of PCV13 following 12 months later by PPS23, versus PPS23 alone) in splenectomised adults.