Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Influenza Viruses
2.2. Vaccine Design, Preparation, and HA Content Quantification
2.3. Animal Vaccination and Infection
2.4. Enzyme-Linked Immunosorbent Assay (ELISA)
2.5. H&E Staining
2.6. Plaque Assay
2.7. Hemagglutination Inhibition Assay (HAI)
2.8. Focus Reduction Assay (FRA)
3. Statistical Analysis
4. Results
4.1. Next Generation H1N1 COBRA Vaccines Protected Mice from Viral Challenge
4.2. Next Generation H1N1 COBRA Vaccines Elicited Broader and Higher HAI Titer in Mice
4.3. Next Generation H1N1 COBRA Vaccines Decreased the Lung Viral Loads after Infection
4.4. Antibodies Elicited by Next Generation of H1N1 COBRA Vaccines Are Mainly against HA Head
4.5. Next Generation H1N1 COBRA Vaccines Elicited a High Level of Neutralizing Antibodies against H1N1 Viruses
4.6. Next Generation H1N1 COBRA Vaccines Protect Animals from Infection with Less Injury and Moderate Inflammation
5. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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1 | 10 | 20 | 30 | 40 | 50 | 60 | ||
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CA/09 MKAILVVLLYTFATANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCK Bris/18 MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCK Y2 MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCK Y4 MKAILVVLLYTFTTANADTLCIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDKHNGKLCK P1 MKARLLVLLCALAATDADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCK X6 MEARLLVLLCAFAATNADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCL Bris/07 MKVKLLVLLCTFTATYADTICIGYHANNSTDTVDTVLEKNVTVTHSVNLLENSHNGKLCL | ||||||||
61 | 70 | 80 | 90 | 100 | 110 | 120 | ||
| | | | | | | | | | | | | | ||
CA/09 LRGVAPLHLGKCNIAGWILGNPECESLSTASSWSYIVETPSSDNGTCYPGDFIDYEELRE Bris/18 LGGVAPLHLGKCNIAGWILGNPECESLSTARSWSYIVETSNSDNGTCYPGDFINYEELRE Y2 LRGVAPLHLGKCNIAGWILGNPECESLSTASSWSYIVETSNSDNGTCYPGDFINYEELRE Y4 LRGVAPLHLGKCNIAGWILGNPECESLSTARSWSYIVETSNSDNGTCYPGDFINYEELRE P1 LKGIAPLQLGKCNIAGWLLGNPECESLLSARSWSYIVETPNSENGTCYPGDFIDYEELRE X6 LKGIAPLQLGNCSVAGWILGNPECELLISKESWSYIVETPNPENGTCYPGYFADYEELRE Bris/07 LKGIAPLQLGNCSVAGWILGNPECELLISKESWSYIVEKPNPENGTCYPGHFADYEELRE | ||||||||
121 | 130 | 140 | 150 | 160 | 170 | 180 | ||
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CA/09 QLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSK Bris/18 QLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLNQ Y2 QLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLSQ Y4 QLSSVSSFERFEIFPKTSSWPNHDSNKGVTAACPHAGAKSFYKNLIWLVKKGNSYPKLNQ P1 QLSSVSSFERFEIFPKESSWPNHNTTKGVTAACSHAGKSSFYRNLLWLTKKGGSYPKLSK X6 QLSSVSSFERFEIFPKESSWPNH-TVTGVSASCSHNGKSSFYRNLLWLTGKNGLYPNLSK Bris/07 QLSSVSSFERFEIFPKESSWPNH-TVTGVSASCSHNGESSFYRNLLWLTGKNGLYPNLSK | ||||||||
181 | 190 | 200 | 210 | 220 | 230 | 240 | ||
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CA/09 SYINDKGKEVLVLWGIHHPSTSADQQSLYQNADAYVFVGSSRYSKKFKPEIAIRPKVRDQ Bris/18 TYINDKGKEVLVLWGIHHPPTTADQQXLYQNADAYVFVGTSRYSKKFKPEIATRPKVRDQ Y2 SYINDKGKEVLVLWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIAIRPKVRDQ Y4 TYINDKGKEVLVLWGIHHPSTTADQQSLYQNADAYVFVGTSRYSKKFKPEIATRPKVRDQ P1 SYVNNKGKEVLVLWGVHHPSTSTDQQSLYQNENAYVSVVSSNYNRRFTPEIAERPKVRGQ X6 SYANNKEKEVLVLWGVHHPPNIGDQRALYHTENAYVSVVSSHYSRKFTPEIAKRPKVRDQ Bris/07 SYANNKEKEVLVLWGVHHPPNIGNQKALYHTENAYVSVVSSHYSRKFTPEIAKRPKVRDQ | ||||||||
241 | 250 | 260 | 270 | 280 | 290 | 300 | ||
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CA/09 EGRMNYYWTLVEPGDKITFEATGNLVVPRYAFAMERNAGSGIIISDTPVHDCNTTCQTPK Bris/18 EGRMNYYWTLVEPGDKITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTAE Y2 EGRMNYYWTLVEPGDKITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPE Y4 EGRMNYYWTLVEPGDKITFEATGNLVVPRYAFTMERNAGSGIIISDTPVHDCNTTCQTPE P1 AGRMNYYWTLLEPGDTIIFEATGNLIAPWYAFALSRGSGSGIITSNASMHECNTKCQTPQ X6 EGRINYYWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGIITSNAPMDECDAKCQTPQ Bris/07 EGRINYYWTLLEPGDTIIFEANGNLIAPRYAFALSRGFGSGIINSNAPMDKCDAKCQTPQ | ||||||||
301 | 310 | 320 | 330 | 340 | 350 | 360 | ||
| | | | | | | | | | | | | | ||
CA/09 GAINTSLPFQNIHPITIGKCPKYVKSTKLRLATGLRNIPSIQSRGLFGAIAGFIEGGWTG Bris/18 GAINTSLPFQNVHPVTIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTG Y2 GAINTSLPFQNVHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTG Y4 GAINTSLPFQNVHPITIGKCPKYVKSTKLRLATGLRNVPSIQSRGLFGAIAGFIEGGWTG P1 GAINSSLPFQNIHPVTIGECPKYVRSTKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTG X6 GAINSSLPFQNVHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTG Bris/07 GAINSSLPFQNVHPVTIGECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTG | ||||||||
361 | 370 | 380 | 390 | 400 | 410 | 420 | ||
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CA/09 MVDGWYGYHHQNEQGSGYAADLKSTQNAIDEITNKVNSVIEKMNTQFTAVGKEFNHLEKR Bris/18 MVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKR Y2 MVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKR Y4 MVDGWYGYHHQNEQGSGYAADLKSTQNAIDKITNKVNSVIEKMNTQFTAVGKEFNHLEKR P1 MIDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVIEKMNTQFTAVGKEFNNLEKR X6 MVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVIEKMNTQFTAVGKEFNKLERR Bris/07 MVDGWYGYHHQNEQGSGYAADQKSTQNAINGITNKVNSVIEKMNTQFTAVGKEFNKLERR | ||||||||
421 | 430 | 440 | 450 | 460 | 470 | 480 | ||
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CA/09 IENLNKKVDDGFLDIWTYNAELLVLLENERTLDYHDSNVKNLYEKVRSQLKNNAKEIGNG Bris/18 IENLNKKVDDGFLDIWTYNAELLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNG Y2 IENLNKKVDDGFLDIWTYNAELLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNG Y4 IENLNKKVDDGFLDIWTYNAELLVLLENERTLDYHDSNVKNLYEKVRNQLKNNAKEIGNG P1 MENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLRNNAKEIGNG X6 MENLNKKVDDGFLDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNG Bris/07 MENLNKKVDDGFIDIWTYNAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNG | ||||||||
481 | 490 | 500 | 510 | 520 | 530 | 540 | ||
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CA/09 CFEFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREEIDGVKLESTRIYQILAIYSTVASS Bris/18 CFEFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREKIDGVKLESTRIYQILAIYSTVASS Y2 CFEFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREKIDGVKLESTRIYQILAIYSTVASS Y4 CFEFYHKCDNTCMESVKNGTYDYPKYSEEAKLNREKIDGVKLESTRIYQILAIYSTVASS P1 CFEFYHKCDNECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVYQILAIYSTVASS X6 CFEFYHKCNNECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVYQILAIYSTVASS Bris/07 CFEFYHKCNDECMESVKNGTYDYPKYSEESKLNREKIDGVKLESMGVYQILAIYSTVASS | ||||||||
541 | 550 | 560 | ||||||
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CA/09 LVLVVSLGAISFWMCSNGSLQCRICI Bris/18 LVLVVSLGAISFWMCSNGSLQCRICI Y2 LVLVVSLGAISFWMCSNGSLQCRICI Y4 LVLVVSLGAISFWMCSNGSLQCRICI P1 LVLLVSLGAISFWMCSNGSLQCRICI X6 LVLLVSLGAISFWMCSNGSLQCRICI Bris/07 LVLLVSLGAISFWMCSNGSLQCRICI |
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Huang, Y.; França, M.S.; Allen, J.D.; Shi, H.; Ross, T.M. Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection. Vaccines 2021, 9, 793. https://doi.org/10.3390/vaccines9070793
Huang Y, França MS, Allen JD, Shi H, Ross TM. Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection. Vaccines. 2021; 9(7):793. https://doi.org/10.3390/vaccines9070793
Chicago/Turabian StyleHuang, Ying, Monique S. França, James D. Allen, Hua Shi, and Ted M. Ross. 2021. "Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection" Vaccines 9, no. 7: 793. https://doi.org/10.3390/vaccines9070793
APA StyleHuang, Y., França, M. S., Allen, J. D., Shi, H., & Ross, T. M. (2021). Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection. Vaccines, 9(7), 793. https://doi.org/10.3390/vaccines9070793