Antibodies Elicited in Response to a Single Cycle Glycoprotein D Deletion Viral Vaccine Candidate Bind C1q and Activate Complement Mediated Neutralization and Cytolysis

• Published in: Viruses Vol. 13; no. 7; p. 1284
• Main Authors: Visciano, Maria Luisa, Mahant, Aakash Mahant, Pierce, Carl, Hunte, Richard, Herold, Betsy C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-06-2021; MDPI
• Subjects: Adjuvants, Immunologic; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibodies, Viral - metabolism; Antibody-Dependent Cell Cytotoxicity; Antigens; C1q; Cell culture; Clinical isolates; complement; Complement Activation; Complement C1q - genetics; Complement C1q - immunology; Complement C1q - metabolism; Complement component C1q; Cytolysis; Cytotoxicity; Female; Gene Deletion; Glycoprotein B; Glycoprotein D; Herpes simplex; herpes simplex viruses; Herpes viruses; Immune serum; Immunization; Immunization, Passive; Latency; Lysates; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Phagocytosis; Proteins; Public health; Vaccination; Vaccines; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; United States > US; C1q; glycoprotein B; vaccines; glycoprotein D; complement; complement-dependent neutralization; complement-dependent cytolysis; herpes simplex viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13071284

Herpes simplex virus (HSV) prevention is a global health priority but, despite decades of research, there is no effective vaccine. Prior efforts focused on generating glycoprotein D (gD) neutralizing antibodies, but clinical trial outcomes were disappointing. The deletion of gD yields a single-cycle candidate vaccine (∆gD-2) that elicits high titer polyantigenic non-gD antibodies that exhibit little complement-independent neutralization but mediate antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Active or passive immunization with DgD-2 completely protects mice from lethal disease and latency following challenge with clinical isolates of either serotype. The current studies evaluated the role of complement in vaccine-elicited protection. The immune serum from the DgD-2 vaccinated mice exhibited significantly greater C1q binding compared to the serum from the gD protein vaccinated mice with infected cell lysates from either serotype as capture antigens. The C1q-binding antibodies recognized glycoprotein B. This resulted in significantly greater antibody-mediated complement-dependent cytolysis and neutralization. Notably, complete protection was preserved when the DgD-2 immune serum was passively transferred into C1q knockout mice, suggesting that ADCC and ADCP are sufficient in mice. We speculate that the polyfunctional responses elicited by DgD-2 may prove more effective in preventing HSV, compared to the more restrictive responses elicited by adjuvanted gD protein vaccines.