A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination.


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It is a sub-study of a previous phase I clinical trial (NCT01986010, registered on November 18th, 2013). The trial was a 2-part, single-blind, randomized, placebo-controlled, dose-escalating study, conducted at 9 clinical sites in the United States. In this sub-study, to characterize the vaccine-induced monoclonal antibodies, we selected, at random, six vaccinated participants from: the 30U intramuscular injection group (n = 3, seronegative, without adjuvant, enrolled in Virginia Commonwealth University), the 30U intradermal injection group (n = 3, seronegative, without adjuvant, enrolled in University of Texas Medical Branch), and the two placebo controls of the intradermal injection group (n = 2, without adjuvant, enrolled in University of Texas Medical Branch)

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The informations were listed in supplementary Table 1. Age range 20s-40s; inculde both male and female, are HCMV seronegative at the time of enrollment of this study.

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The subjects in this study are recruited by two seperate clinical sites, and are HCMV seronegative subjects. Healthy subjects eligible for inclusion in this sub-study were over 18 years of age with bodyweight more than 50 kg and body mass index 19 -32 kg/m2.

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We selected, at random, six vaccinated participants from: the 30U intramuscular injection group (n = 3, seronegative, without adjuvant, enrolled in Virginia Commonwealth University), the 30U intradermal injection group (n = 3, seronegative, without adjuvant, enrolled in University of Texas Medical Branch), and the two placebo controls of the intradermal injection group (n = 2, without adjuvant, enrolled in University of Texas Medical Branch). Human memory B cells were isolated from these subjects, the cells culture and screening of HCMV specific antibodies were performed. We characterized the antibodies for the binding the neutralizing to HCMV.

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Primary outcome: The serum neutralizign titer of the subject after vaccination. Secondary outcome: The binding specificity the neutralizing activity of vaccine induced monoclonal antibodies from the subjects nature research | reporting summary

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