Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate

The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marm...

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Veröffentlicht in:Journal of virology Jg. 88; H. 6; S. 3058
Hauptverfasser: Zapata, Juan C, Goicochea, Marco, Nadai, Yuka, Eyzaguirre, Lindsay M, Carr, Jean K, Tallon, Luke J, Sadzewicz, Lisa, Myers, Garry, Fraser, Claire M, Su, Qi, Djavani, Mahmoud, Lukashevich, Igor S, Salvato, Maria S
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Sprache:Englisch
Veröffentlicht: United States 01.03.2014
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ISSN:1098-5514, 1098-5514
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Abstract The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.
AbstractList The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.
The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.
Author Salvato, Maria S
Lukashevich, Igor S
Djavani, Mahmoud
Zapata, Juan C
Su, Qi
Tallon, Luke J
Eyzaguirre, Lindsay M
Myers, Garry
Sadzewicz, Lisa
Carr, Jean K
Goicochea, Marco
Fraser, Claire M
Nadai, Yuka
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References 11371613 - Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6895-900
11987809 - Curr Top Microbiol Immunol. 2002;262:75-109
23402317 - Virol J. 2013;10:52
11289805 - Virology. 2001 Apr 10;282(2):230-6
23344562 - Viruses. 2013 Jan;5(1):241-78
21262835 - Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2396-401
17378212 - J Vector Borne Dis. 2007 Mar;44(1):1-11
16327776 - Nature. 2006 Jan 19;439(7074):344-8
20200234 - J Virol. 2010 May;84(10):5415-22
1585636 - Virology. 1992 Jun;188(2):600-5
3138361 - Kansenshogaku Zasshi. 1988 Mar;62 Suppl:353-66
15302945 - J Gen Virol. 2004 Sep;85(Pt 9):2515-23
10699137 - Pediatrics. 2000 Mar;105(3):E35
15266969 - Evolution. 2004 Jun;58(6):1185-94
7933157 - J Virol. 1994 Nov;68(11):7649-53
14512579 - J Virol. 2003 Oct;77(20):11296-8
19710144 - J Virol. 2009 Nov;83(21):11330-40
15019244 - Virus Res. 2004 Mar 15;100(2):249-55
19924222 - PLoS Negl Trop Dis. 2009;3(11):e548
11559805 - J Virol. 2001 Oct;75(20):9723-30
18692539 - Vaccine. 2008 Sep 26;26(41):5246-54
3367096 - J Exp Med. 1988 May 1;167(5):1719-24
17143722 - Virus Genes. 2007 Apr;34(2):169-76
15314228 - Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12588-91
19498020 - Blood. 2009 Aug 6;114(6):1196-204
21471230 - J Virol. 2011 Jun;85(12):6024-37
15220423 - J Virol. 2004 Jul;78(14):7498-507
12610166 - J Virol. 2003 Mar;77(6):3882-7
12215495 - Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12938-43
23420494 - J Vaccines Vaccin. 2012 Nov 20;3(7):null
17409137 - J Virol. 2007 Jun;81(12):6482-90
19727424 - Future Virol. 2008 Nov;3(6):553-566
19420075 - J Virol. 2009 Jul;83(14):7029-39
16940530 - J Virol. 2006 Sep;80(18):9192-9
7580496 - BMJ. 1995 Sep 30;311(7009):857-9
20943969 - J Virol. 2010 Dec;84(24):13059-62
20723216 - BMC Evol Biol. 2010;10:253
21085117 - Nature. 2010 Dec 9;468(7325):779-83
2813413 - Proc Natl Acad Sci U S A. 1989 Nov;86(21):8575-9
2705303 - Virology. 1989 Apr;169(2):377-84
16254329 - J Virol. 2005 Nov;79(22):13934-42
21159860 - J Virol. 2011 Mar;85(5):2266-75
16474141 - J Virol. 2006 Mar;80(5):2349-57
16220146 - PLoS Pathog. 2005 Oct;1(2):e11
22216135 - PLoS One. 2011;6(12):e28889
3581899 - Curr Top Microbiol Immunol. 1987;134:69-78
10623742 - J Virol. 2000 Jan;74(2):805-11
References_xml – reference: 14512579 - J Virol. 2003 Oct;77(20):11296-8
– reference: 15266969 - Evolution. 2004 Jun;58(6):1185-94
– reference: 23402317 - Virol J. 2013;10:52
– reference: 23420494 - J Vaccines Vaccin. 2012 Nov 20;3(7):null
– reference: 23344562 - Viruses. 2013 Jan;5(1):241-78
– reference: 15019244 - Virus Res. 2004 Mar 15;100(2):249-55
– reference: 16254329 - J Virol. 2005 Nov;79(22):13934-42
– reference: 20943969 - J Virol. 2010 Dec;84(24):13059-62
– reference: 16327776 - Nature. 2006 Jan 19;439(7074):344-8
– reference: 12215495 - Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12938-43
– reference: 3138361 - Kansenshogaku Zasshi. 1988 Mar;62 Suppl:353-66
– reference: 16940530 - J Virol. 2006 Sep;80(18):9192-9
– reference: 7580496 - BMJ. 1995 Sep 30;311(7009):857-9
– reference: 1585636 - Virology. 1992 Jun;188(2):600-5
– reference: 10699137 - Pediatrics. 2000 Mar;105(3):E35
– reference: 16220146 - PLoS Pathog. 2005 Oct;1(2):e11
– reference: 20200234 - J Virol. 2010 May;84(10):5415-22
– reference: 11289805 - Virology. 2001 Apr 10;282(2):230-6
– reference: 7933157 - J Virol. 1994 Nov;68(11):7649-53
– reference: 15302945 - J Gen Virol. 2004 Sep;85(Pt 9):2515-23
– reference: 19710144 - J Virol. 2009 Nov;83(21):11330-40
– reference: 16474141 - J Virol. 2006 Mar;80(5):2349-57
– reference: 3581899 - Curr Top Microbiol Immunol. 1987;134:69-78
– reference: 20723216 - BMC Evol Biol. 2010;10:253
– reference: 18692539 - Vaccine. 2008 Sep 26;26(41):5246-54
– reference: 3367096 - J Exp Med. 1988 May 1;167(5):1719-24
– reference: 19498020 - Blood. 2009 Aug 6;114(6):1196-204
– reference: 21262835 - Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2396-401
– reference: 22216135 - PLoS One. 2011;6(12):e28889
– reference: 11559805 - J Virol. 2001 Oct;75(20):9723-30
– reference: 11987809 - Curr Top Microbiol Immunol. 2002;262:75-109
– reference: 19420075 - J Virol. 2009 Jul;83(14):7029-39
– reference: 19924222 - PLoS Negl Trop Dis. 2009;3(11):e548
– reference: 2813413 - Proc Natl Acad Sci U S A. 1989 Nov;86(21):8575-9
– reference: 17143722 - Virus Genes. 2007 Apr;34(2):169-76
– reference: 11371613 - Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6895-900
– reference: 19727424 - Future Virol. 2008 Nov;3(6):553-566
– reference: 17409137 - J Virol. 2007 Jun;81(12):6482-90
– reference: 15220423 - J Virol. 2004 Jul;78(14):7498-507
– reference: 21159860 - J Virol. 2011 Mar;85(5):2266-75
– reference: 21085117 - Nature. 2010 Dec 9;468(7325):779-83
– reference: 15314228 - Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12588-91
– reference: 21471230 - J Virol. 2011 Jun;85(12):6024-37
– reference: 17378212 - J Vector Borne Dis. 2007 Mar;44(1):1-11
– reference: 12610166 - J Virol. 2003 Mar;77(6):3882-7
– reference: 10623742 - J Virol. 2000 Jan;74(2):805-11
– reference: 2705303 - Virology. 1989 Apr;169(2):377-84
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Snippet The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by...
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SubjectTerms Animals
Callithrix
Cercopithecus aethiops
Genetic Variation
Humans
Immunity, Cellular
Lassa Fever - immunology
Lassa Fever - prevention & control
Lassa Fever - virology
Lassa virus - genetics
Lassa virus - immunology
Macaca mulatta
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Vaccines, Attenuated - genetics
Vaccines, Attenuated - immunology
Vero Cells
Viral Vaccines - genetics
Viral Vaccines - immunology
Title Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate
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