High Levels of Antibody to Panton-Valentine Leukocidin Are Not Associated with Resistance to Staphylococcus aureus-Associated Skin and Soft-Tissue Infection

Background. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) expressing Panton- Valentine leukocidin (PVL) causes severe skin and soft-tissue infection (SSTI), necrotizing pneumonia, and other invasive infections. The PVL toxin has been implicated as a virulence factor, and antibody to a component of this toxin is under investigation as a vaccine candidate. The role of PVL in pathogenesis remains controversial, and it is unknown whether human serum antibody to PVL modulates infection. Methods. We determined antibody levels to PVL in serum samples from children aged 0-18 years presenting with polymerase chain reaction-confirmed, PVL-positive MRSA-associated SSTI (with or without prior MRSA infection or SSTI), PVL-positive MRSA invasive infection, and PVL-negative MRSA infection, as well as uninfected control subjects. We also measured antibody-mediated neutralization of PVL-induced lysis of human polymorphonuclear cells. Results. Antibody to PVL was present in healthy children reaching adult levels by 4-6 years, with a nadir at 3-11 months likely due to loss of maternal antibody. Children with a primary PVL-positive MRSA infection had moderate levels of antibody to PVL that increased after infection. Children with prior MRSA infection or SSTI had high levels of antibody to PVL after the onset of PVL-positive MRSA infection. There was no increase in antibody to PVL in this population's serum samples after the onset of infection. Serum samples from children with PVL-positive MRSA-associated SSTIs, particularly those with prior MRSA infection or SSTI, and convalescent-phase serum samples from children with invasive PVL-positive MRSA infection potently inhibited PVL-induced lysis of polymorphonuclear cells. Conclusions. Neutralizing antibody to PVL does not protect children against primary or recurrent CA-MRSA-associated SSTI.