Table 7.5.
Single or cocktail of different antibodies and reported efficacy studies in animal models or humans.
| Biothreat agent | Therapeutic target of antibody | Efficacy data | References |
|---|---|---|---|
| Bacterial | |||
| Bacillus anthracis | PA, LF, and EF, and the capsule | Details of the mAbs developed against B. anthracis can be found elsewhere | [132] |
| Burkholderia mallei and Burkholderia pseudomallei | Capsular PS or the LPS | CPS individually, or in combination with an LPS mAb, prevents B. pseudomallei infection in mice. Although both mAbs confer protection when given singly, the combination treatment provided significantly better protection at low doses | [133] |
| Coxiella burnetii | Phase I LPS | 1E4 is an antibody targeting PI-LPS of Cb. Fab1E4 (Fab fragment of 1E4), recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4 | [134] |
| Francisella tularensis | LPS | mAbs against the LPS of F. tularensis LVS could be successfully used to treat LVS-induced pneumonia but not a F. tularensis type A strain. Anti-LVS antibodies failed to protect mice challenged with F. tularensis Schu S4 | [21] |
| Yersinia pestis | Capsid F1 protein and the Lcr V-protein | A synergistic effect was observed when anti-F1-specific human mAb (m252) and two anti-V-specific human mAbs (m253, m254) were combined. Incomplete to complete protection was achieved when m252 was given at different times post challenge | [22] |
| Viral | |||
| Arenaviridae JUNV |
Glycoprotein | Human case reports: convalescent serum therapy controls active infection [135] Guinea Pig: neutralizing antibodies generated by vaccination or monoclonal antibody cocktails are protective |
[136], [137] |
| Arenaviridae Lassa |
Glycoprotein | Human case reports: convalescent plasma therapy–mixed success at controlling infection Guinea Pig: presence of neutralizing GP antibodies can control infection NHP: cocktail of 5 human mAbs conferred high level of protection |
[138], [139] |
| Nanoviridae CCFH |
Unknown | Human case reports: the use of hyperimmunoglobulin obtained from survivor plasma showed modest success | [140], [141], [142] |
| Filoviridae EBOV |
Glycoprotein (Z-EBOV) |
Human clinical trials: ZMapp, c2G4, c4G7, and c13C6 combination cocktail currently being evaluated for safety and efficacy in West Africa and the United States; nine EBOV-infected individuals were administered ZMapp under compassionate use, determined the treatment course to 3 doses at 50 mg/kg at 3 intervals post infection; decreased viral load was observed in all patients (NCT02363322) | [130], [143], [144] |
| Paramyxoviridae Nipah |
F and G envelope glycoproteins | Hamster: IP injection of large amounts of serum from donors receiving antiserum pools of nonspecific neutralizing antibodies can protect against lethal disease Passive administration of murine mAbs against NiV F and G conferred protection |
[145], [146], [147] |
| Poxviridae Monkeypox |
Mature virion and extracellular virion | NHP: prophylactic antibody treatment can protect against severe monkeypox disease in marmoset model | [148] |
| Poxviridae Variola |
Multiple MV, H3, A27, D8, and L1, EV B5, and A33 |
Human case reports: antibodies generated from Vaccinia virus can protect against VAR infection Mice: superior in vivo protection against VACV infection was achieved by administration of a mixture of human mAbs that targeted multiple viral antigens |
[149], [150], [151] |
| Togaviridae Chikungunya |
Glycoprotein E2 subunit |
In vitro: human mAbs 5F10 and 8B10 were isolated from patients infected with CHIKV and found to have neutralizing properties Mice: 4J21 and 5M16 found to be protective; MAb 152 protected mice against was highly effective postexposure treatment of CHIKV infection; MAb 102 and 152 or MAb 152 and 166 cocktails were shown to confer protection in mice exposed to lethal doses of CHIKV and enhanced the window of treatment, as compared to MAb 152 therapy alone NHP: combination use of MAbs 152 and 166 in rhesus macaques noted reduced viral spread and infection with viral RNA persistence |
[152], [153], [154] |
CCFH, Crimean-Congo hemorrhagic fever; CPS, capsular polysaccharide; EF, edema factor; GP, glycoproteins; IP, Intraperitoneal; JUNV, Junin virus; Lcr, low-calcium response; LF, lethal factor; LPS, lipopolysaccharides; LVS, live vaccine strain; mAb, monoclonal antibody; NiV, Nipah virus; NHP, nonhuman primate; PA, protective antigen; PS, polysaccharides; VACV, Vaccinia virus; VAR, Varicella.