A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection
Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection and causes developmental abnormalities, including hearing loss and developmental delay. Although there is no therapy for congenital HCMV disease, there is evidence from both human and animal studies that antibodies can have efficacy in this setting. Such studies have focused exclusively on polyclonal antibodies, in which the targets of protective antibodies are unknown. Guinea pigs have been used as a model of human maternal fetal transmission of infection because of similarities in placental anatomy between human and guinea pig. Furthermore, guinea pig CMV (GPCMV) has been demonstrated to cross the placenta and cause fetal infection and loss, similar to the effects of infection with HCMV. However, the kinetics of maternal and fetal infection in this model has not been carefully investigated. In this work, we have delineated the kinetics of maternal to fetal infection and found that congenital infection is rapid following maternal infection. Importantly, we demonstrate that a monoclonal antibody against a protein critical for viral entry protects pregnant guinea pigs against fetal infection. Thus, our studies may be informative for development of a therapeutic intervention to treat congenital HCMV infection in humans.
Vyšlo v časopise:
A Neutralizing Anti-gH/gL Monoclonal Antibody Is Protective in the Guinea Pig Model of Congenital CMV Infection. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004060
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004060
Souhrn
Human cytomegalovirus (HCMV) is the most common cause of congenital virus infection and causes developmental abnormalities, including hearing loss and developmental delay. Although there is no therapy for congenital HCMV disease, there is evidence from both human and animal studies that antibodies can have efficacy in this setting. Such studies have focused exclusively on polyclonal antibodies, in which the targets of protective antibodies are unknown. Guinea pigs have been used as a model of human maternal fetal transmission of infection because of similarities in placental anatomy between human and guinea pig. Furthermore, guinea pig CMV (GPCMV) has been demonstrated to cross the placenta and cause fetal infection and loss, similar to the effects of infection with HCMV. However, the kinetics of maternal and fetal infection in this model has not been carefully investigated. In this work, we have delineated the kinetics of maternal to fetal infection and found that congenital infection is rapid following maternal infection. Importantly, we demonstrate that a monoclonal antibody against a protein critical for viral entry protects pregnant guinea pigs against fetal infection. Thus, our studies may be informative for development of a therapeutic intervention to treat congenital HCMV infection in humans.
Zdroje
1. BratcherDF, BourneN, BravoFJ, SchleissMR, SlaouiM, et al. (1995) Effect of passive antibody on congenital cytomegalovirus infection in guinea pigs. J Infect Dis 172: 944–950.
2. BourneN, SchleissMR, BravoFJ, BernsteinDI (2001) Preconception immunization with a cytomegalovirus (CMV) glycoprotein vaccine improves pregnancy outcome in a guinea pig model of congenital CMV infection. J Infect Dis 183: 59–64.
3. ChatterjeeA, HarrisonCJ, BrittWJ, BewtraC (2001) Modification of maternal and congenital cytomegalovirus infection by anti-glycoprotein b antibody transfer in guinea pigs. J Infect Dis 183: 1547–1553.
4. StagnoS, WhitleyRJ (1985) Herpesvirus infections of pregnancy. Part I: Cytomegalovirus and Epstein-Barr virus infections. N Engl J Med 313: 1270–1274.
5. RosenthalLS, FowlerKB, BoppanaSB, BrittWJ, PassRF, et al. (2009) Cytomegalovirus shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with congenital infection. Pediatr Infect Dis J 28: 515–520.
6. RossSA, FowlerKB, AshrithG, StagnoS, BrittWJ, et al. (2006) Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J Pediatr 148: 332–336.
7. AlfordCA, StagnoS, PassRF, BrittWJ (1990) Congenital and perinatal cytomegalovirus infections. Rev Infect Dis 12 Suppl 7: S745–753.
8. FowlerKB, StagnoS, PassRF (2003) Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 289: 1008–1011.
9. LilleriD, KabanovaA, LanzavecchiaA, GernaG (2012) Antibodies against neutralization epitopes of human cytomegalovirus gH/gL/pUL128-130-131 complex and virus spreading may correlate with virus control in vivo. J Clin Immunol 32: 1324–1331.
10. LilleriD, KabanovaA, RevelloMG, PercivalleE, SarasiniA, et al. (2013) Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection. PLoS One 8: e59863.
11. NigroG, AdlerSP, La TorreR, BestAM (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353: 1350–1362.
12. SchleissMR (2002) Animal models of congenital cytomegalovirus infection: an overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV). J Clin Virol 25 Suppl 2: S37–49.
13. BakardjievAI, StacyBA, FisherSJ, PortnoyDA (2004) Listeriosis in the pregnant guinea pig: a model of vertical transmission. Infect Immun 72: 489–497.
14. MessA (2007) The Guinea pig placenta: model of placental growth dynamics. Placenta 28: 812–815.
15. BiaFJ, GriffithBP, FongCK, HsiungGD (1983) Cytomegaloviral infections in the guinea pig: experimental models for human disease. Rev Infect Dis 5: 177–195.
16. BiaFJ, SummersWC, FongCK, HsiungGD (1980) New endogenous herpesvirus of guinea pigs: biological and molecular characterization. J Virol 36: 245–253.
17. BiaFJ, MillerSA, DavidsonKH (1984) The guinea pig cytomegalovirus model of congenital human cytomegalovirus infection. Birth Defects Orig Artic Ser 20: 233–241.
18. HsiungGD, ChoiYC, BiaF (1978) Cytomegalovirus infection in guinea pigs. I. Viremia during acute primary and chronic persistent infection. J Infect Dis 138: 191–196.
19. PaglinoJC, BradyRC, SchleissMR (1999) Molecular characterization of the guinea-pig cytomegalovirus glycoprotein L gene. Arch Virol 144: 447–462.
20. SchleissMR (1994) Cloning and characterization of the guinea pig cytomegalovirus glycoprotein B gene. Virology 202: 173–185.
21. BradyRC, SchleissMR (1996) Identification and characterization of the guinea-pig cytomegalovirus glycoprotein H gene. Arch Virol 141: 2409–2424.
22. NozawaN, YamamotoY, FukuiY, KatanoH, TsutsuiY, et al. (2008) Identification of a 1.6 kb genome locus of guinea pig cytomegalovirus required for efficient viral growth in animals but not in cell culture. Virology 379: 45–54.
23. AuerbachM, YanD, FoutsA, XuM, EstevezA, et al. (2013) Characterization of the guinea pig CMV gH/gL/GP129/GP131/GP133 complex in infection and spread. Virology 441: 75–84.
24. BrittWJ, HarrisonC (1994) Identification of an abundant disulfide-linked complex of glycoproteins in the envelope of guinea pig cytomegalovirus. Virology 201: 294–302.
25. SchleissMR, McGregorA, ChoiKY, DateSV, CuiX, et al. (2008) Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome. Virol J 5: 139.
26. OberRJ, RaduCG, GhetieV, WardES (2001) Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies. Int Immunol 13: 1551–1559.
27. WaldmannTA, StroberW (1969) Metabolism of immunoglobulins. Prog Allergy 13: 1–110.
28. BiaFJ, GriffithBP, TarsioM, HsiungGD (1980) Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus. J Infect Dis 142: 732–738.
29. GriffithBP, LavalleeJT, JenningsTA, HsiungGD (1985) Transmission of maternal cytomegalovirus-specific immunity in the guinea pig. Clin Immunol Immunopathol 35: 169–181.
30. MacagnoA, BernasconiNL, VanzettaF, DanderE, SarasiniA, 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.
31. BarriosY, KnorS, LanttoJ, MachM, OhlinM (2007) Clonal repertoire diversification of a neutralizing cytomegalovirus glycoprotein B-specific antibody results in variants with diverse anti-viral properties. Mol Immunol 44: 680–690.
32. MaidjiE, McDonaghS, GenbacevO, TabataT, PereiraL (2006) Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis. Am J Pathol 168: 1210–1226.
33. BoeckhM, BowdenRA, StorerB, ChaoNJ, SpielbergerR, et al. (2001) Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 7: 343–351.
34. BoruckiMJ, SpritzlerJ, AsmuthDM, GnannJ, HirschMS, et al. (2004) A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis. Antiviral Res 64: 103–111.
35. ManleyK, AndersonJ, YangF, SzustakowskiJ, OakeleyEJ, et al. (2011) Human cytomegalovirus escapes a naturally occurring neutralizing antibody by incorporating it into assembling virions. Cell Host Microbe 10: 197–209.
36. FreedDC, TangQ, TangA, LiF, HeX, et al. (2013) Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine. Proc Natl Acad Sci U S A 110: E4997–5005.
37. HartleyJW, RoweWP, HuebnerRJ (1957) Serial propagation of the guinea pig salivary gland virus in tissue culture. Proc Soc Exp Biol Med 96: 281–285.
38. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25: 402–408.
39. SzymczakAL, WorkmanCJ, WangY, VignaliKM, DilioglouS, et al. (2004) Correction of multi-gene deficiency in vivo using a single ‘self-cleaving’ 2A peptide-based retroviral vector. Nat Biotechnol 22: 589–594.
40. KatanoH, SatoY, TsutsuiY, SataT, MaedaA, et al. (2007) Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model. Microbes Infect 9: 183–191.
41. WilliamsDA (1975) The analysis of binary responses from toxicological experiments involving reproduction and teratogenicity. Biometrics 31: 949–952.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2014 Číslo 4
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- The 2010 Cholera Outbreak in Haiti: How Science Solved a Controversy
- Coxsackievirus-Induced miR-21 Disrupts Cardiomyocyte Interactions via the Downregulation of Intercalated Disk Components
- An Overview of Respiratory Syncytial Virus
- , , , Genetic Variability: Cryptic Biological Species or Clonal Near-Clades?