Combinations of Polyclonal or Monoclonal Antibodies to Proteins of the Outer Membranes of the Two Infectious Forms of Vaccinia Virus Protect Mice against a Lethal Respiratory Challenge

Abstract

Previous studies demonstrated that antibodies to live vaccinia virus infection are needed for optimal protection against orthopoxvirus infection. The present report is the first to compare the protective abilities of individual and combinations of specific polyclonal and monoclonal antibodies that target proteins of the intracellular (IMV) and extracellular (EV) forms of vaccinia virus. The antibodies were directed to one IMV membrane protein, L1, and to two outer EV membrane proteins, A33 and B5. In vitro studies showed that the antibodies to L1 neutralized IMV and that the antibodies to A33 and B5 prevented the spread of EV in liquid medium. Prophylactic administration of individual antibodies to BALB/c mice partially protected them against disease following intranasal challenge with lethal doses of vaccinia virus. Combinations of antibodies, particularly anti-L1 and -A33 or -L1 and -B5, provided enhanced protection when administered 1 day before or 2 days after challenge. Furthermore, the protection was superior to that achieved with pooled immune gamma globulin from human volunteers inoculated with live vaccinia virus. In addition, single injections of anti-L1 plus anti-A33 antibodies greatly delayed the deaths of severe combined immunodeficiency mice challenged with vaccinia virus. These studies suggest that antibodies to two or three viral membrane proteins optimally derived from the outer membranes of IMV and EV, may be beneficial for prophylaxis or therapy of orthopoxvirus infections.

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

“…In addition, monkeypox virus (MPXV) DNA priming and protein boosting provided better protection in a MPXV model than either alone [17]. Results obtained by passive administration of polyclonal or monoclonal IgGs to A33, B5 and L1 suggested that antibodies are important for the protection achieved by protein vaccines [18,19].…”

“…This study mimicked our earlier mouse experiments [11], which used B5 in addition to A33 and L1. 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.…”

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

“…Several studies have suggested that antibodies are sufficient to protect against orthopoxvirus infections in mice and monkeys (23,33,34). Here we demonstrate that chimpanzee mAbs against VACV B5 protein (an EV-specific protein) alone are sufficient not only to protect mice from lethal challenge with virulent VACV, but also to confer therapeutic protection of mice when administered 2 days after infection.…”

“…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). In addition, a rat mAb to B5 provided protection in a VACV mouse challenge model (23).…”

Dominance and Diversity in the Primary Human CD4 T Cell Response to Replication-Competent Vaccinia Virus

“…Several potent vaccinia neutralizing membrane Ags have been described (38,39,(47)(48)(49). We expressed and purified three proteins (L1R, A33R, B5R) as extracellular domains and one (A27L) as a full-length construct.…”