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Infection and Immunity, May 1999, p. 2452-2463, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cellular Immune Responses to Neisseria meningitidis in Children

Andrew J. Pollard,1,* Rachel Galassini,1 Eileene M. Rouppe van der Voort,2 Martin Hibberd,1 Robert Booy,1 Paul Langford,1 Simon Nadel,1 Catherine Ison,1 J. Simon Kroll,1 Jan Poolman,2,dagger and Michael Levin1

Departments of Paediatrics and Infectious Diseases & Microbiology, Imperial College School of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom,1 and Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and the Environment, Bilthoven, The Netherlands2

Received 22 September 1998/Returned for modification 2 December 1998/Accepted 5 February 1999

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-gamma ), 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 TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma 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 TH2 cytokine production.

* Corresponding author. Mailing address: Paediatric Infectious Diseases Unit, Imperial College School of Medicine, St. Mary's Hospital, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 171 886 6377. Fax: 44 171 886 6284. E-mail: AJPollard{at}csi.com.

dagger Present address: SmithKline Beecham Biologicals, Rixensart, Belgium.

Infection and Immunity, May 1999, p. 2452-2463, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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