Passive Protection across Subgroups of Alphaviruses by Hyperimmune Non-Cross-Neutralizing Anti-Sindbis Serum

Abstract

Extended hyperimmunization of rabbits with Sindbis (SIN) or Semliki Forest (SF) viruses causes the production of antisera that are cross-reactive with virus-infected cells in antibodydependent, complement-mediated cytotoxicity assays but that do not cross-neutralize viruses in vitro. C3H/HeJ mice given y globulin fractionated from the extended hyperimmune antiserum against SIN, but not control sera, were protected from challenge by 100 LDso of SF, a virus which is in a different subgroup than SIN. All mice survived if the y globulin was given 24 hr before challenge virus and partial protection occurred if the globulin was given 24 hr after the virus. Cobra venom factor treatment of normal C3H mice challenged with SF did not reduce the protection, suggesting that complement was not involved. Methyl palmitate (40 mg/mouse) given before y globulin and virus challenge suppressed macrophage activity and reduced the level of protection 23% in females and 70% in males, Silica treatment (3 mg/mouse) reduced the protection equally in both males and females by 92%. In vitro experiments were done to test if it were possible that cross-antibody-dependent cellular cytotoxicity (ADCC) could accout for the passive crossprotection observed in this system. Cross-ADCC could be demonstrated in vitro at high dilutions of antiserum (1 :25,600). On the basis of the in vitro and in vivo results presented, we suggest that 56

Chikungunya Virus Arthritis in Adult Wild-Type Mice

“…Cross-protection involving alphaviruses that cause lethal encephalitic disease in mice has been extensively studied VOL. 84,2010 CHIKUNGUNYA VIRUS ARTHRITIS IN ADULT WILD-TYPE MICE 8027 (36,81,85). However, cross-protection against arthritis between arthrogenic alphaviruses has not been reported.…”

Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress

“…Although broadly neutralizing MAbs against alphaviruses have not been described, polyclonal antibodies (induced by a CHIKV vaccine candidate) protected against O’nyong’nyong virus (ONNV) infection (Partidos et al, 2012) and convalescent serum from Ross River virus (RRV)-infected mice protected against CHIKV pathogenesis (Gardner et al, 2010). Earlier reports described cross-protection between different alphaviruses using hyperimmune serum (Wust et al, 1987). These studies suggest that conserved epitopes exist across different alphaviruses that are recognized by protective antibodies.…”

Monoclonal antibodies to the matrix (El) glycoprotein of mouse hepatitis virus protect mice from encephalitis

“…Similarly, Harty et a/. Nonneutralizing monoclonal antibodies have also been shown to protect animals against other neurotropic viruses, including Sindbis (29)(30)(31), Semliki Forest (12,32), Western equine encephalitis (33), Venezuelan equine encephalitis (13), St. Louis encephalitis (Id), herpes simplex (34), vesicular stomatitis (15), and yellow fever viruses (7635). In these studies, antibody appeared to block the infection of neurons, while having no effect on the infection of nonneuronal central nervous system cells.…”