Establishment of an ELISpot Assay to Detect Cellular Immunity against S. pneumoniae in Vaccinated Kidney Transplant Recipients

Abstract

In organ transplant recipients, the rate of invasive pneumococcal diseases is 25 times greater than in the general population. Vaccination against S. pneumoniae is recommended in this cohort because it reduces the incidence of this severe form of pneumococcal infection. Previous studies indicate that transplant recipients can produce specific antibodies after pneumococcal vaccination. However, it remains unclear if vaccination also induces specific cellular immunity. In the current study on 38 kidney transplant recipients, we established an interferon-γ ELISpot assay that can detect serotype-specific cellular responses against S. pneumoniae. The results indicate that sequential vaccination with the conjugated vaccine Prevenar 13 and the polysaccharide vaccine Pneumovax 23 led to an increase of serotype-specific cellular immunity. We observed the strongest responses against the serotypes 9N and 14, which are both components of Pneumovax 23. Cellular responses against S. pneumoniae correlated positively with specific IgG antibodies (r = 0.32, p = 0.12). In conclusion, this is the first report indicating that kidney transplant recipients can mount specific cellular responses after pneumococcal vaccination. The ELISpot we established will allow for further investigations. These could help to define, for example, factors influencing specific cellular immunity in immunocompromised cohorts or the duration of cellular immunity after vaccination.

Prospective, Longitudinal Study on Specific Cellular Immune Responses after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Kidney Transplant Recipients

“…In females, cytomegalovirus pp65-specific IL-21 ELISpot responses were higher [23] or antibody titers after vaccination against hepatitis B or SARS-CoV-2 virus were increased [30,37]. However, males showed a trend of higher cellular responses towards pneumococcal antigens [38]. It is, therefore, quite possible that VZV-specific immunity is also sex-dependent.…”

Antibody responses after sequential vaccination with PCV13 and PPSV23 in kidney transplant recipients

“…The pneumococcal vaccine Prevenar 13 contains polysaccharides of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9 V, 14, 18C, 19F, 19A, and 23F), each conjugated to a nontoxic mutant form of diphtheria toxin cross-reactive material 197 (CRM197). It contains 2.2 μg/dose of each of the serotypes, except for serotype 6B at 4.4 μg/dose (0.5 mL) [10].…”

“…However, it is still unclear to what extent serological titers reflect protection against an infection with S. pneumoniae [6]. Studies in kidney transplant recipients (KTR), that examined the humoral response after administration of PCV13 revealed increased functional antibody responses after vaccination [8,10] but could not match the responses in healthy controls [11]. The administration of PPSV23 in kidney KTR also led to a significant increase of antibodies, which was still detectable after a period of 15 months [12,13].…”

Vaccine Response in the Immunocompromised Patient with Focus on Cellular Immunity

“…The establishment of feasible diagnostic methods to assess the cellular immune response is the first step in integrating this approach in the evaluation of vaccine response in immunocompromised patients. In this Special Issue, Gäckler and colleagues developed an interferon-gamma ELISPOT assay sensitive enough to detect vaccine-induced T-cell responses against Streptococcus pneumoniae in 38 clinically stable kidney transplant recipients who received sequential vaccination with the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine [15]. This is the first study that was able to show an increase in serotype-specific cellular immunity after pneumococcal vaccination in organ transplant recipients.…”

“…The authors observed the strongest cellular immune responses against pneumococcal serotypes 9N and 14. The interferon-gamma ELISPOT assay established by Gäckler and colleagues [15] is a technique which could be used for further studies in this area involving larger immunocompromised patient cohorts.…”