Identification of the critical attribute(s) of EBV gp350 antigen required for elicitation of a neutralizing antibody response in vivo

Servat, Esteban; Ro, Bodrey W.; Cayatte, Corinne; Gemmell, Lorraine; Barton, Chris; Rao, Eileen; Lin, Rui; Zuo, Fengrong; Woo, Jennifer; Hayes, Gregory M.

doi:10.1016/j.vaccine.2015.10.024

Cited by 19 publications

(15 citation statements)

References 21 publications

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“…The oral wash procedure, detection and quantitation of EBV DNA, and EIA assays for EBV VCA IgM, VCA IgG, EBNA‐1 IgG and heterophile antibodies were performed as previously described 6 , 17 . Antibodies against gp350 were measured using an EIA developed by Servat et al 18 with minor modifications. The linearity of all antibody assays for both the instrument and subject samples were evaluated for R 2 values using a prepared dye solution as recommended in the Biotek Spectrophotometer Manual (Bio Tek Instruments Inc, Highland Park, VT, USA).…”

Section: Methodsmentioning

confidence: 99%

Prospective studies of infectious mononucleosis in university students

et al. 2016

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We performed an intensive prospective study designed to obtain as much data as possible on the incubation and early illness periods of primary Epstein–Barr virus (EBV) infection. Undergraduate students who lacked EBV antibody and oral EBV DNA (EBV-naive) were seen every 2 weeks during their freshman year. Clinical and behavioral data, oral washes and venous blood were obtained. EBV antibodies were quantified by enzyme immunoassay and viral loads by PCR. During a median 8 months of observation, 14/85 subjects experienced primary EBV infections (24 cases/100 person-years). The only significant risk factor for acquisition of EBV infection was deep kissing (P=0.02). Eleven subjects had infectious mononucleosis with a median duration of 21 days. Two subjects were hospitalized. Infections were initially identified in 12 subjects by finding EBV DNA in oral cells before onset of symptoms and in 2 subjects by symptom reporting. EBV DNA and viral capsid antigen (VCA) IgM and gp350 IgG antibodies were present in the blood before onset of illness. To provide a more robust evaluation of primary EBV infection in undergraduate university students, we combined data on risk factors and antibody responses from this and an earlier study that used the exact same clinical and laboratory methods. The observation that the only significant risk factor for acquisition of EBV infection was deep kissing was confirmed. Most importantly, higher amounts of gp350 antibody correlated significantly with a lower severity of infectious mononucleosis (P<0.0001), which strengthens the rationale for a gp350-based prophylactic EBV vaccine.

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Section: Methodsmentioning

confidence: 99%

Prospective studies of infectious mononucleosis in university students

et al. 2016

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“…In a recent study, we found that mice vaccinated with different gp350 immunogens developed high gp350 ELISA titers relatively early after vaccination but that high gp350 LIPS titers took much longer to develop and required additional doses of immunogen (23). The gp350 LIPS test, an immunoprecipitation assay, is more likely to detect antibody primarily to the native form of the protein, while the ELISA may measure antibodies to both denatured and native forms of the protein (24). In another study, we found that levels of antibody to EBV gp350 measured by an immunoprecipitation assay correlated very closely with levels of neutralizing antibody in human sera (8).…”

Section: Figmentioning

confidence: 99%

Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

Hayes

Liu

et al. 2016

Clin Vaccine Immunol

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Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV.

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“…MAbs to the receptor binding sites of other viruses, including Ebola virus (35), Epstein-Barr virus (EBV) (36), Middle East respiratory syndrome (MERS) virus (37), severe acute respiratory syndrome (SARS) coronavirus (38), influenza virus (39), poliovirus (40), and HIV (41), can potently neutralize virus infection. MAbs DL11 and E317 were previously reported to block both the nectin-1 and HVEM receptor binding sites (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1

Wang

Tomaras

Jegaskanda

et al. 2017

J Virol

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The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus 1 (HSV-1) glycoprotein D (gD) so that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection, as well as antibodies to HSV. We derived monoclonal antibodies (MAbs) from peripheral blood B cells of recipients of the RV144 HIV vaccine and showed that these antibodies neutralized HSV-1 infection in cells expressing HVEM, but not the other major virus receptor, nectin-1. The MAbs mediated antibody-dependent cellular cytotoxicity (ADCC), and mice that received the MAbs and were then challenged by corneal inoculation with HSV-1 had reduced eye disease, shedding, and latent infection. To our knowledge, this is the first description of MAbs derived from human recipients of a vaccine that specifically target the HVEM binding site of gD. In summary, we found that monoclonal antibodies derived from humans vaccinated with the HVEM binding domain of HSV-1 gD (i) neutralized HSV-1 infection in a cell receptor-specific manner, (ii) mediated ADCC, and (iii) reduced ocular disease in virus-infected mice. IMPORTANCE Herpes simplex virus 1 (HSV-1) causes cold sores and neonatal herpes and is a leading cause of blindness. Despite many trials, no HSV vaccine has been approved. Nectin-1 and HVEM are the two major cellular receptors for HSV. These receptors are expressed at different levels in various tissues, and the role of each re-

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Identification of the critical attribute(s) of EBV gp350 antigen required for elicitation of a neutralizing antibody response in vivo

Cited by 19 publications

References 21 publications

Prospective studies of infectious mononucleosis in university students

Prospective studies of infectious mononucleosis in university students

Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1

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