Immunogenicity of the Tetravalent Protein-Conjugated Meningococcal Vaccine in Recipients of Related and Unrelated Allogeneic Hematopoietic Cell Transplants (HCT)

Abstract

Following the successful introduction of the highly immunogenic protein-conjugated Haemophilus influenza and pneumococcal vaccines, Neisseria meningitidis has become the most common cause of bacterial meningitis in the US. Each year, invasive disease (meningitis, sepsis, pneumonia) due to this organism occurs in approximately 500, 000 persons world-wide, including 1400–2800 in the US. Despite rapid institution of appropriate antibiotics, 10%–14% of affected patients die and significant morbidity occurs in up to 20% of survivors. In 2005, the quadrivalent (A, C, Y, W-135) protein conjugated polysaccharide vaccine (MCV4) was approved in the US and recommended for children 11–12 years of age, previously unimmunized adolescents entering college, military recruits, patients with acquired or functional asplenia, and all travelers to hyperendemic or epidemic areas such as sub-Sahara Africa. Improved disease-free survival following HCT has resulted in an increasing number of survivors entering college and traveling abroad. Due to the lack of information on the immunogenicity of this vaccine in transplant survivors, we assessed the responses of 41 patients immunized with MCV4 following an HLA matched related (n=16), mis-matched related (n=2) or unrelated (n=23) HCT. The median age at HCT and at vaccination was 14 years and 18 years, respectively. Patients were transplanted for acute or chronic leukemia (n=28), immunodeficiency disease (n=4), hemoglobinopathy (n=4), HLH (n=1), NHL (n=1), MDS or aplastic anemia (n=3). Fifty percent of patients received an unmodified HCT and four patients were splenectomized prior to vaccination. MCV4 was administered at a median (range) of 3.2 (0.7–12.5) years following transplant. Ninety percent of patients had undetectable titers to all 4 serotypes prior to immunization. Antibody responses were measured by ELISA. Positive response was defined as > 4 ug/ml (serotype A), >5 ug/ml (serotype C), >4 ug/ml (serotype Y), and >3 ug/ml for serotype W-135. Sixty-one percent of patients developed an antibody response to 31 vaccine serotypes, although only 13 developed positive titers to all 4 serotypes. Response to serotypes A, C, Y, and W-135 was observed in 20, 13, 18, and 13 patients, respectively. Responses were significantly poorer in recipients of an unrelated HCT. Of the 7 non-responders who received a second MCV4, 3 of 4 evaluated patients developed titers to all 4 serotypes. This data suggests that although HCT recipients respond to MCV4, the response is sub-optimal, that pre and post vaccine titers should be assessed to ensure adequate protection, and that a booster immunization should be explored in this patient population.