Human T-Cell Responses after Vaccination with the Norwegian Group B Meningococcal Outer Membrane Vesicle Vaccine

We have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group B Neisseria meningitidis outer membrane vesicle (OMV) vaccine. Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46). T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovis BCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination. The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein. The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively. Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose. We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r = 0.50, P < 0.0001, for OMV and PorA). In addition, we observed a progressive increase in the percentage of CD45R0⁺ (memory) CD4-positive T cells (P = 0.002). In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells.

Vaccination with protein antigens will usually result in both a cellular (T-cell) and humoral (B-cell) immune response. For protection against extracellular bacterial infections, like Neisseria meningitidis, bactericidal and opsonic antibodies are of crucial importance, while T cells play a more indirect role by regulating the antibody response in terms of immunoglobulin class switch, affinity maturation, and magnitude of response (1). T cells are also necessary for the induction of immunological memory and can indirectly induce killing of bacteria by activating phagocytes (24).Although polysaccharide-based vaccines against serogroup A and C meningococci are available, this principle cannot be applied to the B serogroup (the most prevalent serogroup in Europe, America, and South Australia) due to low immunogenicity of the B polysaccharide in humans (36). Furthermore, polysaccharides fail to induce T-cell responses and give a poor and short-lived immunity in infants due to their immature immune systems (13, 26). This situation has motivated the development of a Norwegian outer membrane vesicle (OMV) vaccine against group B meningococci based on a B:15:P1.7,16 epidemic strain (44/76) in which the major antigens are outer membrane proteins (11). The porin proteins PorA (class 1) and PorB (class 3) are the most abundant neisserial outer membrane proteins (6). They are present in equal amounts and account for about 70% of the proteins (by weight) in the OMV vaccine (11). This vaccine has previously been shown to induce protection against group B meningococcal disease among teenagers in a large, double-blind, placebo-controlled study (4).To address the question of T-cell-mediated help in vaccine-induced protective B-cell responses against meningococci, we have investigated human T-cell responses during a three-dose regimen with the Norwegian OMV vaccine. Proliferative in vitro T-cell responses against the OMV vaccine and PorA and PorB outer membrane proteins were assayed in peripheral lymphocytes from OMV vaccinees and compared with immunoglobulin G (IgG) antibody responses.