Kinetics of antibody response to influenza vaccination in renal transplant recipients

Abstract

Annual vaccination is routinely used in organ transplant recipients for immunization against seasonal influenza. However, detailed analysis of the kinetics of vaccine-induced immune responses in this population is lacking. In this study, we investigated the kinetics of vaccine strains-specific antibody responses to trivalent influenza vaccine in a group of renal transplant recipients and a control group. First, we found that the geometric mean hemagglutination inhibition titer against all 3 vaccine strains in the transplant cohort was significantly low when compared to control subjects. Next, whereas the control group sera showed significantly higher HA-specific IgG and isotype IgG1 antibodies at all four time points, a similar increase in the transplant group was delayed until day 28. Interestingly, within the transplant group, subjects receiving belatacept/MMF/prednisone-based regimen had significantly lower levels of total IgG and HA-specific IgG when compared to tacrolimus/MMF/prednisone-based regimen. Even though IgG-ASC response in both cohorts peaked at day 7 post-vaccination, the frequency of IgG-ASC was significantly low in the transplant group. Taken together, our studies show delayed kinetics and lower levels of influenza vaccine-specific antibody responses in renal transplant recipients and, more importantly, indicate the need to probe and improve current vaccination strategies in renal transplant recipients.

Keywords: Antibody; Immunosuppression; Influenza; Kidney transplant; Vaccination.

Figure 1:. Serum HI titer in control and transplant groups vaccinated with TIV 2007–08.

Sera collected from control group (filled square), transplant patients (open circle), transplant patients receiving B/M/P (open diamonds) and T/M/P regimen (closed diamonds) at baseline and different time points post-vaccination were assayed for HI titer against 2007–08 vaccine strains: H1N1, A/Solomon Island/3/2006 (A, D); H3N2, A/Wisconsin/67/2005 (B, E); Influenza B virus, B/Malaysia/2506/04 (C, F), as described in the ‘Methods’ section. Data represent GMT values for control and transplant subjects at days 0, 7, 28, 90 post-vaccination.

Figure 2:. Serum total IgG, rHA-specific IgG, rHA-specific IgG1 in control and transplant groups vaccinated with TIV 2007–08.

Sera collected from control group (filled square), transplant patients (open circle), transplant patients receiving B/M/P (open diamonds) and T/M/P regimen (closed diamonds) at baseline and different time points post-vaccination were assayed for total IgG (A, D), rHA-IgG (B, E), and rHA-IgG1 (C, F), as described in the ‘Methods’ section. Data represent mean concentration (μg/mL) of serum antibody for control and transplant subjects at days 0, 7, 28, 90 post-vaccination.

Figure 3:. HA binding rate of serum from control and transplant groups vaccinated with TIV 2007–08.

Sera collected from control (filled square) and transplant patients (filled circle) at baseline and different time points post-vaccination were assayed for HA binding rate against H1-rHA (A) and H3-rHA (B), as described in the ‘Methods’ section. Data represent GMP values for control and transplant subjects at days 0, 7, 28, 90 post-vaccination.

Figure 4:. Ig-ASC in control and transplant groups vaccinated with TIV 2007–08.

PBMCs collected from control and transplant patients at baseline and different time points post-vaccination were analyzed for proportions of Ig G-ASC as described in ‘Methods’ section. Figure 4A shows proportion of IgG-ASC at different time points post-vaccination. Figure 4B shows proportion of IgG-ASC in control group and transplant subjects at day 7 post-vaccination along with limit of detection of the ELISPOT assay. Hatched horizontal line indicates limit of detection of the ELISPOT assay. Data represent influenza-specific IgG-ASC per million PBMC.