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      Subviral particle as vaccine and vaccine platform

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      Current Opinion in Virology
      Elsevier

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          Highlights

          • Large numbers of subviral particles from different viral families have been made.

          • Subviral particles are highly immunogenic and thus excellent vaccine candidates.

          • Subviral particles are noninfectious and safer vaccines than the conventional ones.

          • Subviral particles are capable platforms for foreign antigen presentation.

          • Several subviral particle-based vaccines are commercially available for human use.

          Abstract

          Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.

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          Most cited references121

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          A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

          The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).
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            Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial

            Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.
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              Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial.

              A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.
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                Author and article information

                Contributors
                Journal
                Curr Opin Virol
                Curr Opin Virol
                Current Opinion in Virology
                Elsevier
                1879-6257
                1879-6265
                21 March 2014
                June 2014
                21 March 2014
                : 6
                : 24-33
                Affiliations
                [0005]Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
                Article
                S1879-6257(14)00060-1
                10.1016/j.coviro.2014.02.009
                4072748
                24662314
                22f38e55-8950-4090-8d30-c289625500d4
                Copyright © 2014 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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