Immunogenicity of in vitro folded outer membrane protein PorA of Neisseria meningitidis

C Jansen1, B Kuipers, J van der Biezen

  • 1Department of Molecular Microbiology and Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.

Insights

Researchers developed an endotoxin-free vaccine against serogroup B meningococci. The addition of QuilA adjuvant significantly boosted the immunogenicity of the PorA P1.6 antigen, inducing protective antibodies.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccine Development

Background:

  • PorA P1.6 is a key antigen from Neisseria meningitidis.
  • Previous studies indicated low immunogenicity of purified PorA P1.6 without adjuvants.

Purpose of the Study:

  • To evaluate the immunogenicity of in vitro folded and denatured PorA P1.6 from N. meningitidis strain M990 in mice.
  • To assess the adjuvant effects of QuilA and galE lipooligosaccharide on PorA P1.6 immunogenicity.

Main Methods:

  • In vitro refolding and purification of PorA P1.6 antigen.
  • Immunization of mice with folded/denatured PorA P1.6, with or without QuilA or galE lipooligosaccharide.
  • Analysis of antibody subclasses (IgG2a) and serum bactericidal activity.

Main Results:

  • The immunogenicity of PorA P1.6 was low without adjuvant.
  • QuilA significantly enhanced PorA P1.6 immunogenicity, unlike galE lipooligosaccharide.
  • Immunization with folded PorA P1.6 plus QuilA induced IgG2a antibodies and serum bactericidal activity.

Conclusions:

  • QuilA is an effective adjuvant for enhancing the immunogenicity of PorA P1.6.
  • The developed approach provides a tool for creating endotoxin-free vaccines against serogroup B meningococci.
  • The induction of serum bactericidal activity suggests potential for protective immunity.

Related Concept Videos

Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Bacterial Meningitis01:24

Bacterial Meningitis

Bacterial meningitis is a severe infectious disease involving inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. It occurs when pathogenic bacteria cross the blood–brain barrier and enter the cerebrospinal fluid. Common causative organisms include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. The exact route of entry varies by pathogen and host condition.Routes of Entry...