Immunogenicity of Haemophilus Influenza and Pneumococcal Vaccines in Related and Unrelated Transplant Recipients.
Authors: Pao Mary K. , Papadopoulos Esperanza B. , Kernan Nancy A. , Jakubowski Ann A. , Young James W. , Castro-Malaspina H.R. , Perales Miguel-Angel , O’Reilly Richard J. , Boulad Farid , Prockop Susan , Small Trudy N. 
Published: April 2020

Abstract
Despite advances in post transplant supportive care, invasive infections due to Haemophilus influenza and pneumococcus continue to result in significant morbidity and mortality long after successful HCT. Introduction of the protein-conjugated vaccines in healthy children has been associated with a reduction in invasive infections due to these organisms. Although current post transplant guidelines recommend immunization with the protein-conjugated H. flu vaccine, they still include the use of the 23-valent pure polysaccharide pneumococcal vaccine (PPV), a poor immunogen even in HLA matched sibling transplant recipients. There is limited data on the immunogenicity of any of these vaccines in recipients of an unrelated or T-cell depleted (TCD) HCT. In this study, we evaluated the responses of 270 allogeneic transplant patients who received the H flu conjugate vaccine and initial pneumococcal vaccination with either the 23-valent PPV (n=156) or a series of the protein-conjugated pneumococcal vaccine, Prevnar (n=114). The median age of the 270 patients at the time of HCT was 25.1 years (range, 0.2–69 years). Thirty-eight percent of the patients were children (&lt;18 years of age). Donors were unrelated, HLA-mis-matched related or HLA matched related in 74, 22, and 174 cases, respectively. Seventy percent of patients underwent a TCD HCT. All vaccines were well tolerated. One child had a reversible allergic response to Prevnar. Eighty-seven percent of the patient population responded to the H flu conjugate vaccine, defined as a ≥3 fold rise in titer or seroconversion. Only 24% of patients responded to the 23-valent PPV. There was no significant difference between the response to PPV administered &lt; or &gt; 24 months post HCT (18% vs 28%, p=0.058), nor between children and adults (19% vs 25%, p=0.16). In contrast, 75% of patients were capable of responding to Prevnar, initiated at a median of 16 months post transplant. Response to Prevnar was significantly better in patients &lt; 18 years of age compared to older individuals (85% vs 56%, respectively, p&lt;0.001). There was no significant difference in the ability of children who received an unrelated or HLA matched related HCT to respond to Prevnar (85% vs 86%, p=0.385). In adults, 48% vs 69%, p=0.132) responded to Prevnar following an HLA-matched related or unrelated HCT, respect ively. Forty-one patients who failed to respond to the 23-valent PPV were subsequently immunized with a series of 3 doses of Prevnar administered 2 months apart, resulting in a 76% response rate. These data suggest that continued inclusion of the 23-valent PPV is inadequately protecting patients against a potentially preventable and often fatal disease. Consideration should be given to utilization of Prevnar in the upfront vaccination of children and adults following allogeneic HCT.