Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 31;11(12):e1005316.
doi: 10.1371/journal.ppat.1005316. eCollection 2015 Dec.

New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication

Sarah Knowlson  1 , John Burlison  1 , Elaine Giles  1 , Helen Fox  1 , Andrew J Macadam  1 , Philip D Minor  1
Affiliations

New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication

Sarah Knowlson et al. PLoS Pathog. .

Abstract

Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Base paired stem loop structures in domain V of the 5’ noncoding region of type 3 poliovirus.
Arrow indicates base 472, which is a U in the Sabin type 3 strain but a C in revertants. Red base pairs show substitutions made; either of GC to AU, or mismatches or GU to AU pairs.
Fig 2
Fig 2. Reduction in plaques formed by modified viruses at different temperatures compared to permissive temperature.
a, L20B cells, b, Vero cells, c, Hep2c cells. The type 3 strains Sabin, Saukett, S15, S17, S18 and S19 were examined.
Fig 3
Fig 3. Structure of S19 viruses.
The genetic cassette consisted of S19 where the capsid region was substituted by that for Mahoney or Sabin 1, MEF1 or Sabin 2 or Saukett. A parallel series of viruses was made including a mutation in the 2A protein where an asparagine at residue 18 was replaced by a serine to allow better growth in Vero cells.
Fig 4
Fig 4. Reduction in plaques formed by S19 viruses shown in Fig 3 compared to permissive temperature: a, Hep2c cells, b.MRC5 cells.
c shows the reduction in plaques formed by the S19 N18S series of viruses in Vero cells.
See this image and copyright information in PMC

References

    1. WHO (2015); http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx (Accessed 14th August 2015)
    1. Minor PD.(2012) The polio eradication programme and issues of the endgame. J Gen Virol. 93 457–474 doi: 10.1099/vir.0.036988-0 - DOI - PubMed
    1. WHO(2014a): Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines(inactivated);http://www.who.int/biologicals/vaccines/Annex3_IPV_Recommendations_eng.p...(accessed 14th August 2015)
    1. WHO(2014b). Polio eradication and end game strategic plan. (2015)http://www.polioeradication.org/Portals/0/Document/Resources/StrategyWor... (accessed August 18th 2015)
    1. WHO (2014c) Global action plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of OPV use. Geneva: World Health Organization; 2014, available at: http://www.polioeradication.org/Portals/0/Document/Resources/PostEradica... (accessed 14th August 2015)

Publication types