Cellular Immune Responses toNeisseria meningitidisin Children

Abstract

There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-␥), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a T H 1 response (low IL-10/ IFN-␥ ratio), while older children produced more T H 2 cytokine (higher IL-10/IFN-␥ ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of T H 2 cytokine production.

Improved method to calculate the antibody avidity index

“…Different trials have shown that meningococcal vaccines constituted by OMV are efficient for adults and children older than 2 years of age, but not for infants (16,18). One reason for the failure of the vaccine in young children seems to be the difference in some cytokine production profiles in young children (20). Furthermore, there is also a difference in the quality of the antibodies in young children, since the serum bactericidal activity of IgG is also low (20).…”

Carbohydrate composition of meningococcal lipopolysaccharide modulates the interaction of Neisseria meningitidis with human dendritic cells

“…Genetically determined high IL-10 production has been shown to be a risk factor for fatal outcome of meningococcal disease (Westendorp et al, 1997). Furthermore, it has been shown, that meningococcal infection in young children leads to a low IL-10/IFN-gamma ratio whereas in older children the IL-10/IFN-gamma ratio tends to be higher (Pollard et al, 1999). The reason for low IL-10 levels induced by encapsulated meningococci is the antiphagocytotic property of the capsule.…”

Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa

“…Outer membrane vesicles from MenB were kindly prepared by Dr Jamie Findlow and Dr Ray Borrow, Vaccine Evaluation Unit, Health Protection Agency Northwest (Cartwright et al, 1999;Pollard et al, 1999). OMV were derived from the Norwegian clinical invasive strain H44/76 (B:15:P1.7,16) and the isogenic mutants TR4 (B15:P1.7-8,4) and TR10 (B:15:P1.5-2,10) (Cartwright et al, 1999;Pollard et al, 1999). These differ only in the major outer membrane protein Porin A, and have been selected to be representative of likely colonizing strains in the UK.…”