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Improved intranasal immunization with live-attenuated measles virus after co-inoculation of the lipopeptide MALP-2

Anke Lührmann1, Thomas Tschernig, Reinhard Pabst

  • 1Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany.

Vaccine
|June 21, 2005
PubMed

Insights

Macrophage-activating lipopeptide (MALP-2) stimulates immune responses in cotton rats, enhancing antibody production when co-administered with measles vaccine. However, it did not boost T cell responses or provide protection when measles-specific antibodies were present.

Area of Science:

  • Immunology
  • Vaccinology
  • Infectious Diseases

Background:

  • Macrophage-activating lipopeptide with a molecular weight of 2kDa (MALP-2) is known to activate antigen-presenting cells across species.
  • The immune-stimulating properties of MALP-2 in cotton rats (Sigmodon hispidus) and its impact on vaccine efficacy require further investigation.

Purpose of the Study:

  • To investigate the immune-activating effects of MALP-2 in cotton rats.
  • To evaluate the impact of MALP-2 on the immune response to a live-attenuated measles vaccine virus.
  • To determine the role of MALP-2 in protective immunity against measles virus.

Main Methods:

  • In vitro analysis of cytokine induction (MIP1alpha, MIP1beta, MIP-2, Gro, TNFalpha, IL1alpha, IL6) in cotton rat cells stimulated with MALP-2.
  • Intranasal inoculation of cotton rats with MALP-2 to assess leukocyte migration into the lungs.
  • Co-inoculation of MALP-2 with a live-attenuated measles vaccine virus to measure antibody titers and T cell proliferation.
  • Assessment of protective immunity following MALP-2 immunization in the presence and absence of passively transferred measles virus-specific antibodies.

Main Results:

  • MALP-2 induced the production of key inflammatory cytokines and chemokines in cotton rat cells in vitro.
  • Intranasal administration of MALP-2 led to the recruitment of neutrophils and other leukocytes to the lung lumen and tissue.
  • Co-administration of MALP-2 with the measles vaccine virus resulted in higher neutralizing antibody titers but did not enhance T cell proliferation.
  • MALP-2 immunization conferred protective immunity in the absence of pre-existing measles virus-specific antibodies, but this protection was abrogated in their presence.

Conclusions:

  • MALP-2 effectively activates innate immune cells and promotes leukocyte infiltration in cotton rats.
  • MALP-2 acts as an adjuvant, enhancing the humoral immune response to the measles vaccine virus.
  • The efficacy of MALP-2 as an immunogen is dependent on the immunological context, specifically the presence of pre-existing antibodies.

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