Intranasal vaccination with pneumococcal surface protein A plus poly(I:C) protects against secondary pneumococcal pneumonia in mice.

Effective pneumococcal vaccines are required for preventing secondary bacterial pneumonia, a life-threatening condition, during epidemics of influenza. We examined whether nasal administration of a low dose of pneumococcal surface protein A (PspA) plus polyinosinic-polycytidylic acid (poly(I:C)) could protect against a fatal secondary pneumococcal pneumonia after influenza A virus infection in mice. PspA-specific IgG but not IgA level was higher in the airways and blood of mice nasally administered a low dose of PspA plus poly(I:C) than in mice nasally administered PspA alone or poly(I:C) alone. Binding of PspA-specific IgG increased C3 deposition on the bacterial surface. The survival rate during secondary infection was higher in mice immunized with PspA plus poly(I:C) than in mice immunized with poly(I:C) alone. The significant reduction in bacterial density in the lung and blood was associated with increased survival of immunized mice with secondary pneumonia. Passive transfer of sera from mice immunized with PspA plus poly(I:C) increased the survival of mice infected with secondary pneumonia. Our data suggest that an intranasal PspA vaccine has promising protective effects against secondary pneumonia after influenza and that PspA-specific IgG plays a critical role in this protection.

Serologic and molecular studies of Leptospira and leptospirosis among rats in the Philippines.

Rats are known to be the most important reservoirs and transmission sources of leptospirosis. However, the status of leptospirosis in the Philippines regarding reservoirs and transmission remains unknown. A survey was conducted in Metro Manila and Laguna that analyzed samples obtained from 106 rats. Using the microscopic agglutination test, we found that 92% of rat serum samples were positive for anti-Leptospira antibodies; the most common infecting serovars were Manilae, Hebdomadis, and Losbanos. On the basis of pulsed-field gel electrophoresis and gyrase B gene sequence analyses, four groups of rat kidney isolates were found: L. interrogans serovar Manilae, serovar Losbanos, and serogroup Grippotyphosa, and L. borgpetersenii serogroup Javanica. Most isolates were lethal after experimental infection of golden Syrian hamsters. Results showed that these four Leptospira serovars and serogroups are circulating among rats, and that these animals may be one of the possible transmission sources of leptospirosis in the Philippines.

Intranasal immunization with a mixture of PspA and a Toll-like receptor agonist induces specific antibodies and enhances bacterial clearance in the airways of mice.

To develop an effective nasal vaccine for Streptococcus pneumoniae, the effects of a panel of Toll-like receptor (TLR) agonists in combination with pneumococcal surface protein A (PspA) on induction of PspA-specific antibodies and bacterial clearance were compared in mice. Mice were nasally immunized with 10 microg of TLR agonist (TLR 2-4 and 9) and 2.5 microg of PspA once per week for 3 weeks. Significantly increased levels of PspA-specific immunoglobulin G (IgG) and IgA in the airways and PspA-specific IgG in plasma were found in mice administered PspA plus each TLR agonist, compared with mice administered PspA alone. In a sub-lethal pneumonia model using a serotype 3 pneumococcal strain, bacterial density in the lungs of mice was significantly reduced in mice administered PspA plus each TLR agonist, compared with mice administered either PspA alone or phosphate-buffered saline alone 3h after bacterial challenge. Similarly, enhanced bacterial clearance was found in the nasopharynx of mice administered PspA plus each TLR agonist 1 day after infection with a serotype 19F strain. Our data suggest that PspA-specific antibody induced by nasal immunization with PspA plus TLR agonist is capable of reducing the bacterial load in both the nasopharynx and lungs after challenge with pneumococci with different serotypes. Despite the skewed Th1/Th2 immune responses, the effects of nasal immunization with PspA plus each TLR agonist on bacterial clearances from the lungs 3h after infection and from nasopharynx 1 day after infection in mice were equivalent.