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Cellular immune responses to Neisseria meningitidis in children
A J Pollard1, R Galassini, E M Rouppe van der Voort
1Departments of Paediatrics and Infectious Diseases & Microbiology, Imperial College School of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom. AJPollard@csi.com
Insights
Infant immune responses to serogroup B meningococcal vaccines are poor due to age-related cellular immunity defects. Formulating vaccines to stimulate TH2 cytokine production may improve infant protection against meningococcal disease.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Serogroup B Neisseria meningitidis poses a significant public health threat, necessitating effective vaccines.
- Current outer membrane protein (OMP)-based vaccines are ineffective in infants, despite protecting older children.
- Age-dependent cellular immunity defects are hypothesized to underlie infant vaccine non-responsiveness.
Purpose of the Study:
- To investigate age-dependent differences in cellular immune responses to serogroup B Neisseria meningitidis antigens.
- To explore the role of cytokine production (IFN-gamma, TNF-alpha, IL-10) and T-cell proliferation in infant and child immune responses.
- To inform the development of more effective serogroup B meningococcal vaccines for infants.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from children recovering from meningococcal disease and healthy controls.
- In vitro assays measured PBMC proliferation and cytokine production (IFN-gamma, TNF-alpha, IL-10) in response to meningococcal antigens.
- Cytokine profiles (IL-10/IFN-gamma ratio) were analyzed to assess T-helper cell responses (TH1 vs. TH2).
Main Results:
- Youngest children exhibited a TH1-skewed immune response (low IL-10/IFN-gamma ratio) post-infection.
- Older children showed a trend towards higher T-cell proliferation and a more balanced or TH2-skewed response (higher IL-10/IFN-gamma ratio).
- Immune responses were not significantly influenced by the presence or subtype of specific outer membrane proteins (OMPs).
Conclusions:
- Infant immune systems may require specific stimuli, potentially mimicking the immune response during invasive disease, to mount effective responses to serogroup B meningococcal vaccines.
- Vaccine formulations that promote TH2 cytokine production could enhance cellular immunity in infants.
- Developing infant-specific vaccination strategies is crucial for controlling serogroup B meningococcal infections.
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-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.