Serum antibodies against Panton–Valentine leukocidin in a normal population and during Staphylococcus aureus infection

Abstract

To determine whether Staphylococcus aureus Panton-Valentine leukocidin (PVL) is expressed during human infection, anti-PVL antibody titres were compared in patients with PVL-positive and PVL-negative staphylococcal infections, and in patients with no evidence of S. aureus infection. Patients with PVL-positive strains had higher levels of anti-PVL antibodies than individuals of both control groups. The median anti-PVL titre increased 8.6-fold during the course of PVL-positive infection and 1.4-fold during PVL-negative infection. These results indicate that only PVL-positive S. aureus strains elicit significant anti-PVL antibody production in humans, and demonstrate the production of PVL during PVL-positive S. aureus infection. The protective role of this immune response remains to be established.

Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

“…Of note, other infectious diseases, such as Dengue hemorrhagic fever, have been proposed to have an antibody-dependent enhancement of pathogenesis (34). The findings from our animal studies, along with the high recurrence rate of MRSA infections in humans, often involving the same strain (22)(23)(24)(25)35), and the increased antibody levels to PVL reported after a primary infection (26,27), suggest the need for caution when considering the value of immunization against PVL, due to the potential of antibody to enhance virulence in at least some common settings of S. aureus infection. Susceptibility of PVL + and isogenic Δpvl S. aureus strains to the antimicrobial activity of PMNs.…”

“…Importantly, in this setting, antibody to PVL appeared to decrease the ability of PMNs to control the proliferation of PVLproducing S. aureus, possibly by impairing the process through which these immune cells are activated. These findings likely are highly applicable to human infections with MRSA, given that a 30%-50% recurrence rate within 18 months of MRSA infection has been reported in previously infected humans, usually with the same strain (22)(23)(24)(25), and that individuals with PVL-positive MRSA infections mount potent immune responses to PVL following primary infections (26,27). This finding suggests that humans with recurrent PVL + MRSA infections likely have very high levels of antibody at the onset of infection that nonetheless does nothing to prevent recurrent infection and might even promote reinfection.…”

Enhancement of bacterial virulence by antibody neutralization of immune-activating toxins

“…26,27 These antibodies are likely raised to commensal S. aureus strains demonstrated that pro-inflammatory cytokine release is activated in cells, [10][11][12] suggesting that in early stages of infection when PVL levels are low, the primary response to this toxin is activation of innate immunity and increased resistance to infection.…”

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

“…[29][30][31] Anti-PVL antibodies enhance the virulence of PVL producing strains by neutralizing this pro-inflammatory effect at sub-cytolytic concentrations, thus limiting their role in prevention of disease. 32 In observational studies, individuals infected with PVL-positive S. aureus strains have higher levels of anti-PVL antibodies compared to patients with PVL-negative S. aureus infections or no S. aureus infection, 33 but a protective role of this immune response in humans has not been established. In contrast, some murine models suggest that anti-PVL antibodies may play a role in reducing the severity or protecting against infection.…”