Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51

Three prophylactic vaccines are approved to protect against HPV infections. These vaccines are highly immunogenic. The most recent HPV vaccine, Gardasil-9, protects against HPV types associated with ~90% of cervical cancer (worldwide). Thus, ~10% of HPV-associated cancers are not protected by Gardas...

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Main Authors: Rashi Yadav, Lukai Zhai, Nitesh K. Kunda, Pavan Muttil, Ebenezer Tumban
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/6/1113
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author Rashi Yadav
Lukai Zhai
Nitesh K. Kunda
Pavan Muttil
Ebenezer Tumban
author_facet Rashi Yadav
Lukai Zhai
Nitesh K. Kunda
Pavan Muttil
Ebenezer Tumban
author_sort Rashi Yadav
collection DOAJ
description Three prophylactic vaccines are approved to protect against HPV infections. These vaccines are highly immunogenic. The most recent HPV vaccine, Gardasil-9, protects against HPV types associated with ~90% of cervical cancer (worldwide). Thus, ~10% of HPV-associated cancers are not protected by Gardasil-9. Although this is not a large percentage overall, the HPV types associated with 10% of cervical cancer not protected by the current vaccine are significantly important, especially in HIV/AIDS patients who are infected with multiple HPV types. To broaden the spectrum of protection against HPV infections, we developed mixed MS2-L2 VLPs (MS2-31L2/16L2 VLPs and MS2-consL2 (69-86) VLPs) in a previous study. Immunization with the VLPs neutralized/protected mice against infection with eleven high-risk HPV types associated with ~95% of cervical cancer and against one low-risk HPV type associated with ~36% of genital warts & up to 32% of recurrent respiratory papillomatosis. Here, we report that the mixed MS2-L2 VLPs can protect mice from three additional HPV types: HPV51, which is associated with ~0.8% of cervical cancer; HPV6, which is associated with up to 60% of genital warts; HPV5, which is associated with skin cancers in patients with epidermodysplasia verruciformis (EV). Overall, mixed MS2-L2 VLPs can protect against twelve HPV types associated with ~95.8% of cervical cancers and against two HPV types associated with ~90% of genital warts and >90% recurrent respiratory papillomatosis. Additionally, the VLPs protect against one of two HPV types associated with ~90% of HPV-associated skin cancers in patients with EV. More importantly, we observed that mixed MS2-L2 VLPs elicit protective antibodies that last over 9 months. Furthermore, a spray-freeze-dried formulation of the VLPs is stable, immunogenic, and protective at room temperature and 37 °C.
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spelling doaj.art-643b2d2f45bc43ff94fd16f38a8f271d2023-11-21T23:30:58ZengMDPI AGViruses1999-49152021-06-01136111310.3390/v13061113Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51Rashi Yadav0Lukai Zhai1Nitesh K. Kunda2Pavan Muttil3Ebenezer Tumban4Department of Biological Sciences, Michigan Technological University, Houghton, MI 49931, USADepartment of Biological Sciences, Michigan Technological University, Houghton, MI 49931, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USADepartment of Biological Sciences, Michigan Technological University, Houghton, MI 49931, USAThree prophylactic vaccines are approved to protect against HPV infections. These vaccines are highly immunogenic. The most recent HPV vaccine, Gardasil-9, protects against HPV types associated with ~90% of cervical cancer (worldwide). Thus, ~10% of HPV-associated cancers are not protected by Gardasil-9. Although this is not a large percentage overall, the HPV types associated with 10% of cervical cancer not protected by the current vaccine are significantly important, especially in HIV/AIDS patients who are infected with multiple HPV types. To broaden the spectrum of protection against HPV infections, we developed mixed MS2-L2 VLPs (MS2-31L2/16L2 VLPs and MS2-consL2 (69-86) VLPs) in a previous study. Immunization with the VLPs neutralized/protected mice against infection with eleven high-risk HPV types associated with ~95% of cervical cancer and against one low-risk HPV type associated with ~36% of genital warts & up to 32% of recurrent respiratory papillomatosis. Here, we report that the mixed MS2-L2 VLPs can protect mice from three additional HPV types: HPV51, which is associated with ~0.8% of cervical cancer; HPV6, which is associated with up to 60% of genital warts; HPV5, which is associated with skin cancers in patients with epidermodysplasia verruciformis (EV). Overall, mixed MS2-L2 VLPs can protect against twelve HPV types associated with ~95.8% of cervical cancers and against two HPV types associated with ~90% of genital warts and >90% recurrent respiratory papillomatosis. Additionally, the VLPs protect against one of two HPV types associated with ~90% of HPV-associated skin cancers in patients with EV. More importantly, we observed that mixed MS2-L2 VLPs elicit protective antibodies that last over 9 months. Furthermore, a spray-freeze-dried formulation of the VLPs is stable, immunogenic, and protective at room temperature and 37 °C.https://www.mdpi.com/1999-4915/13/6/1113human papillomavirusesthermostable vaccinesprotectionMS2 bacteriophagevirus-like particlesspray-freeze-drying
spellingShingle Rashi Yadav
Lukai Zhai
Nitesh K. Kunda
Pavan Muttil
Ebenezer Tumban
Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
Viruses
human papillomaviruses
thermostable vaccines
protection
MS2 bacteriophage
virus-like particles
spray-freeze-drying
title Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
title_full Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
title_fullStr Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
title_full_unstemmed Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
title_short Mixed Bacteriophage MS2-L2 VLPs Elicit Long-Lasting Protective Antibodies against HPV Pseudovirus 51
title_sort mixed bacteriophage ms2 l2 vlps elicit long lasting protective antibodies against hpv pseudovirus 51
topic human papillomaviruses
thermostable vaccines
protection
MS2 bacteriophage
virus-like particles
spray-freeze-drying
url https://www.mdpi.com/1999-4915/13/6/1113
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AT pavanmuttil mixedbacteriophagems2l2vlpselicitlonglastingprotectiveantibodiesagainsthpvpseudovirus51
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