Activation of Cell‐Mediated Immunity Following Immunization with Pneumococcal Conjugate or Polysaccharide Vaccine^*

Abstract

The immunogenicity of pneumococcal polysaccharide (PS) vaccines can be improved by conjugating PS to a polypeptide carrier that alters the immune response from T-cell independent to T-cell dependent. In order to study the influence of PS or protein antigens as inducers of cell-mediated responses, 30 adults were immunized with a 23-valent pneumococcal PS vaccine (PS-group) or an 11-valent, tetanus and diphtheria mixed carrier conjugate vaccine with (adjuvant group) or without aluminium adjuvant (nonadjuvant group). Cell-mediated responses were analyzed on days 0, 14 and 28 after vaccination by measuring lymphocyte proliferation and production of interferon (IFN)-g (Th1 marker) or interleukin (IL)-4 and IL-5 (Th2 markers) cytokines after in vitro stimulation with the PS and protein components of the vaccines. Tetanus and diphtheria proteins were the main inducers of lymphocyte proliferative and cytokine responses. Conjugate vaccines induced increased proliferative responses to the tetanus or diphtheria protein, but not to the PS components. In the PS-group, a lymphocyte proliferative response to protein antigens was not observed. The number of antigen-specific and nonspecific IFN-g-secreting cells detected by ELISPOT tended to increase in all three groups in response to protein or to PS antigen. No major differences were detected in the number of IL-4-secreting cells measured 14 and 28 days after vaccination. The conjugate vaccine with adjuvant was associated with Th2 type of activation indicated by an enhanced IL-5 secretion in response to the tetanus and diphtheria protein antigens.

Elderly-Onset Neuromyelitis Optica which Developed after the Diagnosis of Prostate Adenocarcinoma and Relapsed after a 23-Valent Pneumococcal Polysaccharide Vaccination

“…Conversely, the 23-valent pneumococcal polysaccharide vaccine produces a humoral response: inducing the production of antibody from B lymphocytes in the absence of help from T lymphocytes. This vaccine does not induce interferon-gamma or interleukin-4 and interleukin-5 cytokines related to T lymphocytes (7). The levels of complement C3 and C4 are reported to reveal no change after a 23-valent pneumococcal polysaccharide vaccination (8) and the present patient revealed the same results.…”

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

“…It is assumed that the increased immunogenicity of PS antigens after conjugation to proteins is due to the induction of carrier-specific T cells that provide help to B cells that have internalized and processed the PS conjugate complex and presented peptides of the carrier in MHC class II molecules [40]. Induction of carrier-specific T cells after immunization with conjugate vaccines has been demonstrated both in mice [10,13], human adults ( [11,12] and Ingolfsdottir, G. et al unpublished data) and children [41]. Furthermore, it has been demonstrated that co-stimulatory signals through CD28-B7, and interaction between CD40-CD40L is required for optimal PS-specific B-cell responses after immunization with conjugate vaccines [14].…”

“…The absence of T cell help in Ab responses to PS is due to their inability to associate with MHC class II molecules on APC [8,9]. However, conjugation of PS to protein carriers allows T cell help through recruitment of carrier-specific T cells [10][11][12][13][14] and makes the PPS immunogenic in early infancy (reviewed in [15]). Protective immunity against both invasive disease [16,17] and otitis media [18] has been demonstrated after vaccination of infants with pneumococcal conjugate vaccines.…”

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

“…Wuorimaa et al found that in vitro stimulation of human peripheral blood cells with caps-PS induced activation of IFN-+ -secreting lymphocytes [23]. Caps-PS was also shown to induce IL-6 in in vitro cultured human lymphocytes [24].…”