Галерея 3165217

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Clin Vaccine Immunol

v.18(9); 2011 Sep

PMC3165217

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Clin Vaccine Immunol. 2011 Sep; 18(9): 1536–1542.
Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298
* Corresponding author. Mailing address: Department of Pediatrics, Virginia Commonwealth University School of Medicine, P.O. Box 980163, Richmond, VA 23298-0163. Phone: (804) 828-0132. Fax: (804) 828-6455. E-mail: ude.ucv@yovcmm .
Received 2011 May 3; Revisions requested 2011 Jun 14; Accepted 2011 Jul 14.
Copyright © 2011, American Society for Microbiology. All Rights Reserved.
a Subjects A1 to A9 are non-daycare-associated adults; subjects M1 to M7 are daycare-associated mothers.
b <35, low; 35 to 45, medium; >45, high.
c Determined by immunoblotting. +, antibodies detected; −, antibodies not detected.
e Ranges are inverse logs of the mean log(IC 50 ) ± standard error of the mean log(IC 50 ).
g Shading indicates results for individuals with high immunity to CMV.
1.
Adler B., et al. 2006. Role of human cytomegalovirus UL131A in cell type-specific virus entry and release . J. Gen. Virol. 87 :2451–2460 [ PubMed ] [ Google Scholar ]
2.
Adler S. P., Marshall B. 2007. Cytomegalovirus infections . Pediatr. Rev. 28 :92–100 [ PubMed ] [ Google Scholar ]
3.
Adler S. P., et al. 1995. Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age . J. Infect. Dis. 171 :26–32 (Erratum, 171: 1080.) [ PubMed ] [ Google Scholar ]
4.
Arvin A. M., Fast P., Myers M., Plotkin S., Rabinovich R. 2004. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee . Clin. Infect. Dis. 39 :233–239 [ PubMed ] [ Google Scholar ]
5.
Cui X., Meza B. P., Adler S. P., McVoy M. A. 2008. Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection . Vaccine 26 :5760–5766 [ PMC free article ] [ PubMed ] [ Google Scholar ]
6.
Dollard S. C., Grosse S. D., Ross D. S. 2007. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection . Rev. Med. Virol. 17 :355–363 [ PubMed ] [ Google Scholar ]
7.
Gerna G., et al. 2008. Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection . J. Gen. Virol. 89 :853–865 [ PubMed ] [ Google Scholar ]
8.
Granade T. C., et al. 2002. Influence of host factors on immunoglobulin G concentration in oral fluid specimens . Clin. Diagn. Lab. Immunol. 9 :194–197 [ PMC free article ] [ PubMed ] [ Google Scholar ]
9.
Hahn G., et al. 2004. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes . J. Virol. 78 :10023–10033 [ PMC free article ] [ PubMed ] [ Google Scholar ]
10.
Jacobson M. A., et al. 2009. A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain) . Vaccine 27 :1540–1548 [ PubMed ] [ Google Scholar ]
11.
Macagno A., et al. 2010. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex . J. Virol. 84 :1005–1013 [ PMC free article ] [ PubMed ] [ Google Scholar ]
12.
Marshall B. C., Adler S. P. 2003. Avidity maturation following immunization with two human cytomegalovirus (CMV) vaccines: a live attenuated vaccine (Towne) and a recombinant glycoprotein vaccine (gB/MF59) . Viral Immunol. 16 :491–500 [ PubMed ] [ Google Scholar ]
13.
Mortimer P. P., Parry J. V. 1991. Non-invasive virological diagnosis: are saliva and urine specimens adequate substitutes for blood? Rev. Med. Virol. 1 :73–78 [ Google Scholar ]
14.
Pass R. F., et al. 2009. Vaccine prevention of maternal cytomegalovirus infection . N. Engl. J. Med. 360 :1191–1199 [ PMC free article ] [ PubMed ] [ Google Scholar ]
15.
Patrone M., et al. 2005. Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion . J. Virol. 79 :8361–8373 [ PMC free article ] [ PubMed ] [ Google Scholar ]
16.
Ryckman B. J., et al. 2008. Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells . J. Virol. 82 :60–70 [ PMC free article ] [ PubMed ] [ Google Scholar ]
17.
Saccoccio F. M., et al. 2011. Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells . Vaccine 29 :2705–2711 [ PMC free article ] [ PubMed ] [ Google Scholar ]
18.
Shen S., Wang S., Britt W. J., Lu S. 2007. DNA vaccines expressing glycoprotein complex II antigens gM and gN elicited neutralizing antibodies against multiple human cytomegalovirus (HCMV) isolates . Vaccine 25 :3319–3327 [ PubMed ] [ Google Scholar ]
19.
Shimamura M., Mach M., Britt W. J. 2006. Human cytomegalovirus infection elicits a glycoprotein M (gM)/gN-specific virus-neutralizing antibody response . J. Virol. 80 :4591–4600 [ PMC free article ] [ PubMed ] [ Google Scholar ]
20.
Stratton K. R., Durch S. J., Lawrence R. S. (ed.) 2000. Vaccines for the 21st century: a tool for decisionmaking . National Academy Press, Washington, DC [ Google Scholar ]
21.
Tamura T., Chiba S., Chiba Y., Nakao T. 1980. Virus excretion and neutralizing antibody response in saliva in human cytomegalovirus infection . Infect. Immun. 29 :842–845 [ PMC free article ] [ PubMed ] [ Google Scholar ]
22.
Waissbluth J. G., Langman M. J. 1971. ABO blood groups, secretor status, salivary protein, and serum and salivary immunoglobulin concentrations . Gut 12 :646–649 [ PMC free article ] [ PubMed ] [ Google Scholar ]
23.
Wang D., Shenk T. 2005. Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism . J. Virol. 79 :10330–10338 [ PMC free article ] [ PubMed ] [ Google Scholar ]
24.
Wang D., Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism . Proc. Natl. Acad. Sci. U. S. A. 102 :18153–18158 [ PMC free article ] [ PubMed ] [ Google Scholar ]
25.
Wang J. B., Adler S. P. 1996. Salivary antibodies to cytomegalovirus (CMV) glycoprotein B accurately predict CMV infections among preschool children . J. Clin. Microbiol. 34 :2632–2634 [ PMC free article ] [ PubMed ] [ Google Scholar ]
26.
Wang J. B., et al. 1996. Mucosal antibodies to human cytomegalovirus glycoprotein B occur following both natural infection and immunization with human cytomegalovirus vaccines . J. Infect. Dis. 174 :387–392 [ PubMed ] [ Google Scholar ]
27.
Wang J. B., McVoy M. A. 2008. Mutagenesis of the murine cytomegalovirus M56 terminase gene . J. Gen. Virol. 89 :2864–2868 [ PMC free article ] [ PubMed ] [ Google Scholar ]
28.
Wilms I. R., Best A. M., Adler S. P. 2008. Cytomegalovirus infections among African-Americans . BMC Infect. Dis. 8 :107. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Articles from Clinical and Vaccine Immunology : CVI are provided here courtesy of American Society for Microbiology (ASM)
6.
Dollard S. C., Grosse S. D., Ross D. S. 2007. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection . Rev. Med. Virol. 17 :355–363 [ PubMed ] [ Google Scholar ] [ Ref list ]
20.
Stratton K. R., Durch S. J., Lawrence R. S. (ed.) 2000. Vaccines for the 21st century: a tool for decisionmaking . National Academy Press, Washington, DC [ Google Scholar ] [ Ref list ]
4.
Arvin A. M., Fast P., Myers M., Plotkin S., Rabinovich R. 2004. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee . Clin. Infect. Dis. 39 :233–239 [ PubMed ] [ Google Scholar ] [ Ref list ]
3.
Adler S. P., et al. 1995. Immunity induced by primary human cytomegalovirus infection protects against secondary infection among women of childbearing age . J. Infect. Dis. 171 :26–32 (Erratum, 171: 1080.) [ PubMed ] [ Google Scholar ] [ Ref list ]
14.
Pass R. F., et al. 2009. Vaccine prevention of maternal cytomegalovirus infection . N. Engl. J. Med. 360 :1191–1199 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
16.
Ryckman B. J., et al. 2008. Characterization of the human cytomegalovirus gH/gL/UL128-131 complex that mediates entry into epithelial and endothelial cells . J. Virol. 82 :60–70 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
24.
Wang D., Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism . Proc. Natl. Acad. Sci. U. S. A. 102 :18153–18158 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
11.
Macagno A., et al. 2010. Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex . J. Virol. 84 :1005–1013 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
5.
Cui X., Meza B. P., Adler S. P., McVoy M. A. 2008. Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection . Vaccine 26 :5760–5766 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
9.
Hahn G., et al. 2004. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes . J. Virol. 78 :10023–10033 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
15.
Patrone M., et al. 2005. Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion . J. Virol. 79 :8361–8373 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
2.
Adler S. P., Marshall B. 2007. Cytomegalovirus infections . Pediatr. Rev. 28 :92–100 [ PubMed ] [ Google Scholar ] [ Ref list ]
26.
Wang J. B., et al. 1996. Mucosal antibodies to human cytomegalovirus glycoprotein B occur following both natural infection and immunization with human cytomegalovirus vaccines . J. Infect. Dis. 174 :387–392 [ PubMed ] [ Google Scholar ] [ Ref list ]
25.
Wang J. B., Adler S. P. 1996. Salivary antibodies to cytomegalovirus (CMV) glycoprotein B accurately predict CMV infections among preschool children . J. Clin. Microbiol. 34 :2632–2634 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
28.
Wilms I. R., Best A. M., Adler S. P. 2008. Cytomegalovirus infections among African-Americans . BMC Infect. Dis. 8 :107. [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
10.
Jacobson M. A., et al. 2009. A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain) . Vaccine 27 :1540–1548 [ PubMed ] [ Google Scholar ] [ Ref list ]
12.
Marshall B. C., Adler S. P. 2003. Avidity maturation following immunization with two human cytomegalovirus (CMV) vaccines: a live attenuated vaccine (Towne) and a recombinant glycoprotein vaccine (gB/MF59) . Viral Immunol. 16 :491–500 [ PubMed ] [ Google Scholar ] [ Ref list ]
17.
Saccoccio F. M., et al. 2011. Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells . Vaccine 29 :2705–2711 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
23.
Wang D., Shenk T. 2005. Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism . J. Virol. 79 :10330–10338 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
27.
Wang J. B., McVoy M. A. 2008. Mutagenesis of the murine cytomegalovirus M56 terminase gene . J. Gen. Virol. 89 :2864–2868 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
21.
Tamura T., Chiba S., Chiba Y., Nakao T. 1980. Virus excretion and neutralizing antibody response in saliva in human cytomegalovirus infection . Infect. Immun. 29 :842–845 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
13.
Mortimer P. P., Parry J. V. 1991. Non-invasive virological diagnosis: are saliva and urine specimens adequate substitutes for blood? Rev. Med. Virol. 1 :73–78 [ Google Scholar ] [ Ref list ]
22.
Waissbluth J. G., Langman M. J. 1971. ABO blood groups, secretor status, salivary protein, and serum and salivary immunoglobulin concentrations . Gut 12 :646–649 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
8.
Granade T. C., et al. 2002. Influence of host factors on immunoglobulin G concentration in oral fluid specimens . Clin. Diagn. Lab. Immunol. 9 :194–197 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]
1.
Adler B., et al. 2006. Role of human cytomegalovirus UL131A in cell type-specific virus entry and release . J. Gen. Virol. 87 :2451–2460 [ PubMed ] [ Google Scholar ] [ Ref list ]
7.
Gerna G., et al. 2008. Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection . J. Gen. Virol. 89 :853–865 [ PubMed ] [ Google Scholar ] [ Ref list ]
18.
Shen S., Wang S., Britt W. J., Lu S. 2007. DNA vaccines expressing glycoprotein complex II antigens gM and gN elicited neutralizing antibodies against multiple human cytomegalovirus (HCMV) isolates . Vaccine 25 :3319–3327 [ PubMed ] [ Google Scholar ] [ Ref list ]
19.
Shimamura M., Mach M., Britt W. J. 2006. Human cytomegalovirus infection elicits a glycoprotein M (gM)/gN-specific virus-neutralizing antibody response . J. Virol. 80 :4591–4600 [ PMC free article ] [ PubMed ] [ Google Scholar ] [ Ref list ]

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Congenital cytomegalovirus (CMV) disease is the leading cause of permanent disability in neonates in the United States. Neutralizing antibodies in saliva may protect against maternal CMV infection by blocking viral entry into oral epithelial cells, but the antibody response to CMV in the saliva following natural infection is not well characterized. Saliva specimens from naturally infected individuals were tested for CMV-neutralizing activity using epithelial and fibroblast cells. Saliva from seronegative adults had no inherent anti-CMV activity. Neutralizing activity of saliva from naturally infected adults was not detectable using fibroblast cells, and saliva from young children, adolescents, and Towne vaccine recipients did not have activity using either cell type. However, when using epithelial cells, neutralizing activity was present in saliva from 50% of seropositive adults, correlated with serum-neutralizing activity, and was more prevalent in mothers of children in day care than in non-day care-associated adults. Three day care mothers with high salivary neutralizing activities (>1:20) had exceptionally high serum-neutralizing titers (3- to 8-fold higher than typical seropositives) and were immunoblot positive for serum antibodies to the epithelial entry mediator UL130. These results suggest that salivary neutralizing activities are attainable by induction of high serum IgG levels and could be utilized to evaluate candidate cytomegalovirus vaccines.
Cytomegalovirus (CMV) is the leading cause of congenital abnormalities in the United States, causing serious permanent disabilities in greater than 5,500 children annually. Approximately 13% of congenitally infected infants are symptomatic at birth, and of those born infected but asymptomatic, 17 to 20% will later develop permanent sequelae, such as hearing loss and cognitive impairment. Sensorineural hearing loss is the most common disability found in congenitally infected infants, affecting about 36% of symptomatic and 12% of asymptomatic infants ( 6 ). Due to the high incidence of permanent sequelae from congenital CMV, development of a CMV vaccine has been deemed a national priority by the Institute of Medicine ( 20 ).
Two experimental vaccines have been evaluated for efficacy in humans. The Towne live attenuated vaccine has been used in nearly 1,000 volunteers with no serious side effects ( 4 ). The Towne vaccine induces neutralizing antibodies and T cell responses, but when used at a low dose failed to protect seronegative mothers of viruric children from acquiring CMV ( 3 ). The glycoprotein B (gB)/MF59 vaccine, comprised of recombinant gB adjuvanted with MF59, induces gB-specific antibodies superior to those induced with natural infection and in a recent trial was 50% effective in protecting seronegative women from primary infection ( 14 ).
Neutralizing antibody is important for vaccine protection. CMV infection induces two neutralizing activities in serum. Antibodies directed mostly against gB impair viral entry into both fibroblasts and epithelial cells, whereas antibodies that target gH/gL/UL128-131, a complex comprised of gH, gL, UL128, UL130, and UL131 (originally known as UL131A) that is dispensable for fibroblast entry but critical for epithelial cell entry ( 16 , 24 ), potently and selectively impair viral entry into epithelial cells ( 11 ). Following natural infection, the later activity is dominant, as serum-neutralizing titers measured with epithelial cells are on average 48-fold higher than those measured using fibroblasts ( 5 ). In co
Огромные силиконовые титяндры
Одна раскрепощенная блондинка принимает в себя три члена и получает удовольствие от их проникновения
Кончил на лицо красивой рыжей шлюхе с бритой пиздой

Галерея 3165217

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