Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation

Abstract

Summary:Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day À1 and 50 and whether the levels can be further improved by donor vaccination on day À20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day À20, recipient on days À1, þ 50 and þ 365 (D À20 R À1,50,365 ); (2) donor nil, recipient on days À1, þ 50 and þ 365 (D N R À1,50,365 ); or (3) donor nil, recipient on day þ 365 (D N R 365 ). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D À20 R À1,50,365 patients, intermediate in the D N R À1,50,365 patients and the lowest in the D N R 365 patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days À1 and 50 improves antibody levels and that donor vaccination on day À20 further improves the levels. In contrast, neither recipient immunization on days À1 and 50 nor donor immunization on day À20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens. 3-6 Antibody levels can be improved either by the administration of immunoglobulin or by vaccination. The administration of immunoglobulin may decrease the rates of some infections at the time of immunoglobulin administration, but may hamper reconstitution of antibody immunity and thus increase infection rates after the immunoglobulin has been discontinued. 6 The vaccination can improve pathogen-specific immunity both at the time of vaccination as well as years after vaccination. However, vaccination during the first year after transplantation leads to only minor increases in specific antibody levels. Moderate to marked increases in specific antibody levels during the first year after transplant were achieved when both the donor and the recipient were immunized 7-10 days before transplantation and the recipient was boosted at 3 and 6 months after transplantation. 7,8 Presumably this happened because large numbers of antigen-specific lymphocytes were generated in the donors and because these lymphocytes (transferred with the graft) or their progeny proliferated and differentiated upon encounter with the antigen injected to the recipient 7-10 days before transplant and at 3 and 6 months after transplant.We set out to compare the following three vaccination strategies: (1) donor vaccination on day À20 (20 days before transplant) with recipient vaccination on days À1, þ 50 and þ 365 (D À20 R À1,50,365 ); (2) no donor vaccination and recipient vaccination on days À1, þ 50 and þ 365 (D N R À1,50,365 ) and (3) a conventional strategy of no don...

Pretransplant vaccinations in allogeneic stem cell transplantation donors and recipients: an often-missed opportunity for immunoprotection?

“…Moreover, pretransplant immunizations in both donor and recipient were found to potentiate Ab response post transplantation. 17 However, Storek et al 19 did not find that preHSCT donor and recipient vaccination resulted in detectable levels of antibodies. As HbsAg is a poorly immunogenic protein neoantigen, it is conceivable that repetitive donor vaccination may result in higher Ab titers and thus higher transfer of immunity.…”

“…36 Donor immunization, however, can boost protective immunity for immunocompromised patients. 37 Storek et al 19 determined that Ab levels post transplant are improved by vaccinating the donor (20 days before transplant) as well as the recipient (1 day before transplant and 50 days post transplant) for H. influenzae. Parkkali et al 20 also confirmed that Hib Ab concentrations were significantly higher 12 months post transplant when the patient received a graft from a vaccinated donor.…”

“…As HbsAg is a poorly immunogenic protein neoantigen, it is conceivable that repetitive donor vaccination may result in higher Ab titers and thus higher transfer of immunity. 19 Donor and recipient vaccination preSCT may result in further immunoprotection against HBV.…”

“…Several studies have shown that donor vaccination improves the likelihood of transfer of immunity. [17][18][19][20] Storek et al 19 determined that Ab levels post HSCT are improved by vaccinating the donor (20 days before HSCT) as well as the recipient (1 day before HSCT and 50 days post HSCT) for tetanus. Parkkali et al 20 found that donor vaccination resulted in significantly higher Ab concentrations for diphtheria at 6 and 13 months post HSCT.…”

Control of hepatitis B virus infection in hematopoietic stem cell recipients after receiving grafts from vaccinated donors

“…3,[5][6][7][8][9] However, protection from reactivation depended on vigorous HBV immunity in the donor. 3,10 Therefore, donors should optimally receive more than one immunization, a rather high Ag dose and a highly immunogenic vaccine. As clearance from HBV infection is dependent on effective T-cell immunity, the protection of recipients can be estimated better if their HBV-specific cellular immune response is known.…”