Immunization of Rabbits with Recombinant Human Cytomegalovirus Trimeric versus Monomeric gH/gL Protein Elicits Markedly Higher Titers of Antibody and Neutralization Activity
Congenital human cytomegalovirus (HCMV) infection and HCMV infection of immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery,...
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| Veröffentlicht in: | International journal of molecular sciences 2019-06, Vol.20 (13), p.3158 |
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| creator | Cui, Xinle Cao, Zhouhong Wang, Shuishu Flora, Michael Adler, Stuart P McVoy, Michael A Snapper, Clifford M |
| description | Congenital human cytomegalovirus (HCMV) infection and HCMV infection of immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery, play critical roles in HCMV fusion and entry into host cells. HCMV gB and gH/gL have been reported to elicit potent neutralizing antibodies. Recently, the gB/gH/gL complex was identified in the envelope of HCMV virions, and 16-50% of the total gH/gL bound to gB, forming the gB/gH/gL complex. These findings make the gB/gH/gL a unique HCMV vaccine candidate. We previously reported the production of HCMV trimeric gB and gH/gL heterodimers, and immunization with a combination of trimeric gB and gH/gL heterodimers elicited strong synergistic HCMV-neutralizing activity. To further improve the immunogenicity of gH/gL, we produced trimeric gH/gL. Rabbits immunized with HCMV trimeric gH/gL induced up to 38-fold higher serum titers of gH/gL-specific IgG relative to HCMV monomeric gH/gL, and elicited ~10-fold higher titers of complement-dependent and complement-independent HCMV-neutralizing activity for both epithelial cells and fibroblasts. HCMV trimeric gH/gL in combination with HCMV trimeric gB would be a novel promising HCMV vaccine candidate that could induce highly potent neutralizing activities. |
| doi_str_mv | 10.3390/ijms20133158 |
| format | Article |
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HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery, play critical roles in HCMV fusion and entry into host cells. HCMV gB and gH/gL have been reported to elicit potent neutralizing antibodies. Recently, the gB/gH/gL complex was identified in the envelope of HCMV virions, and 16-50% of the total gH/gL bound to gB, forming the gB/gH/gL complex. These findings make the gB/gH/gL a unique HCMV vaccine candidate. We previously reported the production of HCMV trimeric gB and gH/gL heterodimers, and immunization with a combination of trimeric gB and gH/gL heterodimers elicited strong synergistic HCMV-neutralizing activity. To further improve the immunogenicity of gH/gL, we produced trimeric gH/gL. Rabbits immunized with HCMV trimeric gH/gL induced up to 38-fold higher serum titers of gH/gL-specific IgG relative to HCMV monomeric gH/gL, and elicited ~10-fold higher titers of complement-dependent and complement-independent HCMV-neutralizing activity for both epithelial cells and fibroblasts. HCMV trimeric gH/gL in combination with HCMV trimeric gB would be a novel promising HCMV vaccine candidate that could induce highly potent neutralizing activities.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20133158</identifier><identifier>PMID: 31261659</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antibodies, Neutralizing - immunology ; Antiviral agents ; Bands ; CHO Cells ; Clinical trials ; Congenital diseases ; Cricetinae ; Cricetulus ; Cytomegalovirus ; Cytomegalovirus Vaccines - immunology ; Deoxyribonucleic acid ; DNA ; GL protein ; Graft rejection ; Graft-versus-host reaction ; Grafting ; Grafts ; Hematopoietic stem cells ; Hepatitis ; Humans ; Immunization ; Immunoglobulins ; Immunosuppressive agents ; Infections ; Monoclonal antibodies ; Pneumonitis ; Proteins ; Rabbits ; Stem cell transplantation ; Stem cells ; Transplantation ; Transplants & implants ; Vaccines ; Vaccines, Synthetic - immunology ; Viral Envelope Proteins - chemistry ; Viral Envelope Proteins - genetics ; Viral Envelope Proteins - immunology ; Viremia</subject><ispartof>International journal of molecular sciences, 2019-06, Vol.20 (13), p.3158</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-79dee98f689fdf85edfa13967325514e175d062bafb43dd96a14b4ed086f2c033</citedby><cites>FETCH-LOGICAL-c412t-79dee98f689fdf85edfa13967325514e175d062bafb43dd96a14b4ed086f2c033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651862/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651862/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31261659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cui, Xinle</creatorcontrib><creatorcontrib>Cao, Zhouhong</creatorcontrib><creatorcontrib>Wang, Shuishu</creatorcontrib><creatorcontrib>Flora, Michael</creatorcontrib><creatorcontrib>Adler, Stuart P</creatorcontrib><creatorcontrib>McVoy, Michael A</creatorcontrib><creatorcontrib>Snapper, Clifford M</creatorcontrib><title>Immunization of Rabbits with Recombinant Human Cytomegalovirus Trimeric versus Monomeric gH/gL Protein Elicits Markedly Higher Titers of Antibody and Neutralization Activity</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Congenital human cytomegalovirus (HCMV) infection and HCMV infection of immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery, play critical roles in HCMV fusion and entry into host cells. HCMV gB and gH/gL have been reported to elicit potent neutralizing antibodies. Recently, the gB/gH/gL complex was identified in the envelope of HCMV virions, and 16-50% of the total gH/gL bound to gB, forming the gB/gH/gL complex. These findings make the gB/gH/gL a unique HCMV vaccine candidate. We previously reported the production of HCMV trimeric gB and gH/gL heterodimers, and immunization with a combination of trimeric gB and gH/gL heterodimers elicited strong synergistic HCMV-neutralizing activity. To further improve the immunogenicity of gH/gL, we produced trimeric gH/gL. Rabbits immunized with HCMV trimeric gH/gL induced up to 38-fold higher serum titers of gH/gL-specific IgG relative to HCMV monomeric gH/gL, and elicited ~10-fold higher titers of complement-dependent and complement-independent HCMV-neutralizing activity for both epithelial cells and fibroblasts. HCMV trimeric gH/gL in combination with HCMV trimeric gB would be a novel promising HCMV vaccine candidate that could induce highly potent neutralizing activities.</description><subject>Animals</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antiviral agents</subject><subject>Bands</subject><subject>CHO Cells</subject><subject>Clinical trials</subject><subject>Congenital diseases</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus Vaccines - immunology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>GL protein</subject><subject>Graft rejection</subject><subject>Graft-versus-host reaction</subject><subject>Grafting</subject><subject>Grafts</subject><subject>Hematopoietic stem cells</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoglobulins</subject><subject>Immunosuppressive agents</subject><subject>Infections</subject><subject>Monoclonal antibodies</subject><subject>Pneumonitis</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - 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immunology</topic><topic>Antiviral agents</topic><topic>Bands</topic><topic>CHO Cells</topic><topic>Clinical trials</topic><topic>Congenital diseases</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus Vaccines - immunology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>GL protein</topic><topic>Graft rejection</topic><topic>Graft-versus-host reaction</topic><topic>Grafting</topic><topic>Grafts</topic><topic>Hematopoietic stem cells</topic><topic>Hepatitis</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunoglobulins</topic><topic>Immunosuppressive agents</topic><topic>Infections</topic><topic>Monoclonal antibodies</topic><topic>Pneumonitis</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><topic>Vaccines</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Viral Envelope Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Xinle</au><au>Cao, Zhouhong</au><au>Wang, Shuishu</au><au>Flora, Michael</au><au>Adler, Stuart P</au><au>McVoy, Michael A</au><au>Snapper, Clifford M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunization of Rabbits with Recombinant Human Cytomegalovirus Trimeric versus Monomeric gH/gL Protein Elicits Markedly Higher Titers of Antibody and Neutralization Activity</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-06-28</date><risdate>2019</risdate><volume>20</volume><issue>13</issue><spage>3158</spage><pages>3158-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Congenital human cytomegalovirus (HCMV) infection and HCMV infection of immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery, play critical roles in HCMV fusion and entry into host cells. HCMV gB and gH/gL have been reported to elicit potent neutralizing antibodies. Recently, the gB/gH/gL complex was identified in the envelope of HCMV virions, and 16-50% of the total gH/gL bound to gB, forming the gB/gH/gL complex. These findings make the gB/gH/gL a unique HCMV vaccine candidate. We previously reported the production of HCMV trimeric gB and gH/gL heterodimers, and immunization with a combination of trimeric gB and gH/gL heterodimers elicited strong synergistic HCMV-neutralizing activity. To further improve the immunogenicity of gH/gL, we produced trimeric gH/gL. Rabbits immunized with HCMV trimeric gH/gL induced up to 38-fold higher serum titers of gH/gL-specific IgG relative to HCMV monomeric gH/gL, and elicited ~10-fold higher titers of complement-dependent and complement-independent HCMV-neutralizing activity for both epithelial cells and fibroblasts. HCMV trimeric gH/gL in combination with HCMV trimeric gB would be a novel promising HCMV vaccine candidate that could induce highly potent neutralizing activities.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31261659</pmid><doi>10.3390/ijms20133158</doi><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Antibodies, Neutralizing - immunology Antiviral agents Bands CHO Cells Clinical trials Congenital diseases Cricetinae Cricetulus Cytomegalovirus Cytomegalovirus Vaccines - immunology Deoxyribonucleic acid DNA GL protein Graft rejection Graft-versus-host reaction Grafting Grafts Hematopoietic stem cells Hepatitis Humans Immunization Immunoglobulins Immunosuppressive agents Infections Monoclonal antibodies Pneumonitis Proteins Rabbits Stem cell transplantation Stem cells Transplantation Transplants & implants Vaccines Vaccines, Synthetic - immunology Viral Envelope Proteins - chemistry Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Viremia |
| title | Immunization of Rabbits with Recombinant Human Cytomegalovirus Trimeric versus Monomeric gH/gL Protein Elicits Markedly Higher Titers of Antibody and Neutralization Activity |
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