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Increased protection against pneumococcal disease by mucosal administration of conjugate vaccine plus interleukin-12

Joyce M Lynch1, David E Briles, Dennis W Metzger

  • 1Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208, USA.

Infection and Immunity
|July 23, 2003
PubMed

Insights

Intranasal pneumococcal conjugate vaccines with interleukin-12 (IL-12) adjuvant enhance immune responses and protect against invasive disease and bacterial carriage. This approach improves protection beyond current intramuscular vaccines.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Streptococcus pneumoniae causes respiratory infections, with nasal mucosa as the primary entry route.
  • Current pneumococcal conjugate vaccines offer limited protection (50-60%) against bacterial carriage.
  • Need for improved vaccine strategies targeting mucosal immunity and carriage.

Purpose of the Study:

  • To evaluate intranasal (i.n.) conjugate vaccine delivery with interleukin-12 (IL-12) as a mucosal adjuvant.
  • To assess the vaccine's efficacy in enhancing systemic and mucosal immune responses against Streptococcus pneumoniae.
  • To determine protection against invasive infection and bacterial carriage.

Main Methods:

  • Mice were immunized intranasally with conjugate vaccine and IL-12.
  • Immune responses measured included cytokine mRNA (gamma interferon, IL-10), antibody levels (IgG2a, IgA), and opsonic activity.
  • Mice were challenged intraperitoneally or intranasally with Streptococcus pneumoniae.
  • Studies included genetically modified mice lacking IgA expression.

Main Results:

  • IL-12 treated mice showed increased lung and splenic gamma interferon and IL-10 mRNA.
  • High levels of serum IgG2a and respiratory IgA, along with enhanced opsonic activity, were observed.
  • Intranasal vaccination resulted in 75% survival against intraperitoneal challenge and reduced upper respiratory tract bacterial colonies after intranasal challenge.
  • Intramuscular vaccination showed no significant difference in carriage, unlike intranasal vaccination.
  • Pneumococcus-specific IgA was crucial for bacterial clearance from the upper respiratory tract.

Conclusions:

  • Intranasal vaccination with IL-12 adjuvant effectively enhances both systemic and mucosal immune responses to pneumococci.
  • This strategy provides significant protection against invasive pneumococcal infection and reduces bacterial carriage.
  • Intranasal vaccine delivery holds promise for improved prevention of pneumococcal diseases, including carriage.

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