Table 1.
Studies implicating host FcR-mediated functions in protection against HSV and HCMV infections.
| Virus | Model | Functions implicated | Relevant observations | References |
|---|---|---|---|---|
| HSV-2 | Mice | ADCC | Passively transferred non-neutralizing monoclonal antibodies with known ADCC function, measured by 51Cr release, protected complement-deficient mice from HSV-2 challenge | (29) |
| HSV-1 | Mice | FcR-mediated functions | Passive immunization with IgG, as compared to F(ab')2 treatment, reduced viral titer, and viral spread in HSV-1 challenged mice | (30) |
| HSV-2 | Humans | ADCC | High maternal or neonatal anti-HSV ADCC antibody levels, measured by infected cell release of 51Cr label, or high neonatal antiviral neutralizing levels were independently associated with an absence of disseminated HSV infection | (31) |
| HSV-1 | Mice | ADCC | Antibodies against HSV gB or gD given with human mononuclear cells protected against lethal challenge in neonatal mice with HSV-1, and protection was associated with monoclonal ADCC activity | (32) |
| HSV-1 | Mice | ADCC | Both neutralization and ADCC activity were independently associated with in vivo protection against HSV-1 challenge | (33) |
| HSV-2 | Humans | ADCC | Among HSV-2 gB-2 and gD-2-vaccinated subjects, low ADCC responses were implicated in poor vaccine efficacy against HSV-2 | (34) |
| HSV-2 | Mice | ADCC | Antibody dependent protection against genital HSV-2 infection occurs in an Fcγ-receptor dependent mechanism | (35) |
| HSV-1 | Mice | ADCC | HSV-1 FcγR protected the virus by blocking IgG Fc-mediated complement activation and NK cell-mediated ADCC in vivo. | (36) |
| HSV-2 | Mice and guinea pigs | Not specified | Neutralization and IFNγ T cell responses did not correlate with vaccine efficacy for HSV-2 subunit vaccines containing gD or gB alone or in combination, together with CpG adjuvant | (37) |
| HSV-2 | Mice | ADCC | The majority of sera collected from mice immunized with mature gG-2 plus CpG adjuvant showed complement-mediated cytolysis and macrophage-mediated ADCC, measured by infected cell release of 51Cr label, but not neutralization | (38) |
| HSV-1 and HSV-2 | Mice | ADCC | Single-cycle HSV ΔgD-2 vaccine conferred protection against skin challenge with clinical isolates, as well as rapid clearance and elimination of latent virus. Protection was associated with target cell killing | (39) |
| HSV-1 and HSV-2 | Mice | ADCC, ADCP | Single-cycle HSV ΔgD-2 vaccine conferred protection against skin challenge with clinical isolates, and protection was associated with activation of HSV-specific murine FcγRIII and FcγRIV | (40) |
| HSV-1 | Human mAbs | ADCC | mAbs derived from humans vaccinated with the HVEM binding domain of HSV-1 gD mediated neutralization and ADCC, measured by NK cell activation, and reduced ocular disease in infected mice | (41) |
| HSV-1 and HSV-2 | Mice | ADCC, ADCP | Single-cycle HSV ΔgD-2 vaccine conferred protection against skin challenge with clinical isolates, and protection was associated with activation of HSV-specific murine FcγRIV | (42) |
| HCMV | Mice | Not specified | Prophylactic treatment with HCMV gB-specific neutralizing and non-neutralizing antibodies protected equally against CMV challenge. In the setting of established infection, neutralizing and non-neutralizing antibodies provided protection, with neutralizing antibodies being superior | (43) |
| HCMV | Humans | ADCP | An HCMV gB vaccine that afforded 50% protection in a clinical trial in post-partum women elicited limited neutralization of autologous virus and negligible neutralization of heterologous strains but robust ADCP | (10) |
| HCMV | Humans | ADCP | An HCMV gB vaccine that afforded partial protection in a clinical trial in transplant recipients elicited limited neutralization of autologous virus and negligible neutralization of heterologous strains but robust ADCP | (11) |
gB, glycoprotein B; gD, glycoprotein D; IFNγ, interferon-gamma; gG, glycoprotein G; HSV ΔgD-2, HSV deleted of glycoprotein D.