Vaccination With a Replication-Defective Cytomegalovirus Vaccine Elicits a Glycoprotein B-Specific Monoclonal Antibody Repertoire Distinct From Natural Infection

Authors

Sarah M Valencia
Eric Rochat
Melissa J Harnois
Maria Dennis
Helen S Webster
Bhavna Hora
Amit Kumar
Hsuan-Yuan Sherry Wang
Leike Li
Daniel Freed
Ningyan Zhang
Zhiqiang An
Dai Wang
Sallie R Permar

Publication Date

10-10-2023

Journal

NPJ Vaccines

Abstract

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59. We characterize gB-specific monoclonal antibodies isolated from individuals vaccinated with a disabled infectious single cycle (DISC) CMV vaccine, V160, and compare these to the gB-specific monoclonal antibody repertoire isolated from naturally-infected individuals. We find that vaccination with V160 resulted in gB-specific antibodies that bound homogenously to gB expressed on the surface of a cell in contrast to antibodies isolated from natural infection which variably bound to cell-associated gB. Vaccination resulted in a similar breadth of gB-specific antibodies, with binding profile to gB genotypes 1-5 comparable to that of natural infection. Few gB-specific neutralizing antibodies were isolated from V160 vaccinees and fewer antibodies had identifiable gB antigenic domain specificity compared to that of naturally-infected individuals. We also show that glycosylation of gB residue N73 may shield binding of gB-specific antibodies.

Keywords

Immunology, Vaccines

Comments

Supplementary Materials