Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin

Abstract

In the event of smallpox bioterrorism, widespread vaccination may be required. Vaccinia immune globulin (VIG) has been used to treat complications from the smallpox vaccine. While the potency of VIG was defined by its ability to neutralize intracellular mature virus, a second form of vaccinia called the extracellular enveloped virus (EEV) is critical for virus spread in the host. The B5R-protein is one of many EEV-specific proteins. Immunoprecipitation and ELISA revealed that VIG recognizes the B5R-protein. An EEV plaque-reduction assay using a recombinant vaccinia that lacks the majority of the extracellular domain of B5R showed that the ability of VIG to neutralize EEV is principally directed at B5R. In addition, absorbing out the anti-B5R antibody present in VIG through the addition of recombinant B5R protein abrogated VIG's ability to significantly neutralize wild-type EEV. This work demonstrates the prominent role of B5R as a target of EEV-neutralizing activity of human antibodies.

Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges

“…Recombinant B5 protein [11,14] as well as antibodies to B5 [18,19] can provide protection in the VACV mouse pneumonia model. In addition, B5 is the major target of EV neutralizing antibody in human VACV immune globulin [61], though antibody to B5 is not necessarily the most protective in vivo. Also, VACV B5 has a slightly greater amino acid identity (96%) to the MPXV homolog than VACV A33, which has 93% identity.…”

Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus

“…Recent studies showed that anti-B5 in VIG was responsible for most of the neutralizing activity against EV as measured by a plaque reduction assay (21). To date, rat and mouse anti-B5 neutralizing mAbs have been reported (20,22), and the epitopes recognized by mouse mAbs have been mapped to the border of SCR1-SCR2 and͞or the stalk of B5 (20).…”

Disparity between Levels of In Vitro Neutralization of Vaccinia Virus by Antibody to the A27 Protein and Protection of Mice against Intranasal Challenge

“…For example, passive immunization with antibodies to the EV proteins A33 and B5 is protective (42). Of the two, however, only the anti-B5 antibody neutralizes EV (6). Thus, the present and previous findings raise questions regarding the basis of protection by antibody and whether it occurs by direct virus neutralization or involves complement and Fc-receptor interactions.…”