Expression of codon optimized major capsid protein (L1) of human papillomavirus type 16 and 18 in Pichia pastoris; purification and characterization of the virus-like particles

Rao, N. Hanumantha; Babu, P. Baji; Lingala, Rajendra; Sriraman, Rajan; Pang, Yuxi; Schiller, John T.; Srinivasan, V.A.

doi:10.1016/j.vaccine.2011.07.071

Cited by 40 publications

(17 citation statements)

References 29 publications

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“…Phase I clinical trials of a capsomere-based vaccine are anticipated in the near future [76]. Alternatives for lowering the cost of manufacturing being investigated include the generation of the L1 VLPs in alternative yeast production systems, such as Pichia pastoris [79], or in plants [80]. Live recombinant viral and bacterial vectors, such a measles [81], adeno-associated virus [82] and Salmonella typhi [83], expressing L1 have also generated promising results in preclinical studies.…”

Section: Second-generation Vaccinesmentioning

confidence: 99%

A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

Schiller

Castellsagué

Garland

2012

Vaccine

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659

532

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End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as high value public health interventions and justify their widespread implementation to prevent anogenital HPV infections and their associated neoplasia. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012.

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Section: Second-generation Vaccinesmentioning

confidence: 99%

A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

Schiller

Castellsagué

Garland

2012

Vaccine

Self Cite

659

532

View full text Add to dashboard Cite

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“…To date, expression of HPV in yeast is well documented, with varying degrees of success, and involves only expression of HPV L1 protein, and HPV L1 is also always targeted to the cytosol, from where it is then purified (Patel et al ., ; Bazan et al ., ; Kim et al ., ; Hanumantha Rao et al ., ). This prompted us to investigate whether we could clone and express a chimeric version of HPV 16 consisting of both structural proteins L1 and L2.…”

Section: Discussionmentioning

confidence: 97%

Comparing cytosolic expression to peroxisomal targeting of the chimeric L1/L2 (ChiΔH‐L2) gene from human papillomavirus type 16 in the methylotrophic yeasts Pichia pastoris and Hansenula polymorpha

Smith

Burke

Bredell

et al. 2012

Yeast

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The chimeric ChiΔH-L2 gene from human papillomavirus type 16, consisting of structural proteins L1 and L2, was successfully expressed in the cytosol of both Pichia pastoris and Hansenula polymorpha during methanol induction. In addition, a novel approach was employed whereby ChiΔH-L2 was targeted to the peroxisome using peroxisomal targeting sequence 1 (PTS1) to compare ChiΔH-L2 yields in the peroxisome vs the cytosol. The ChiΔH-L2 gene was yeast-optimized and cloned into plasmids aimed at genomic integration. Levels of intracellular ChiΔH-L2 accumulation in the cytosol were highest in P. pastoris KM71 strain KMChiΔH-L2 (1.43 mg/l), compared to the maximum production level of 0.72 mg/l obtained with H. polymorpha. ChiΔH-L2 targeting to the peroxisome was successful; however, it appeared to negatively affect ChiΔH-L2 production in both P. pastoris and H. polymorpha.

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“…This protein induced high EHV-1 ELISA and virus neutralizing antibodies and also protected BALB/c mice which had been challenged with infection (Balamurugan et al, 2003;Dummer et al, 2009). L1 protein of Human papilloma virus (HPV) type 6 expressed in P. pastoris, has helped the HPV vaccine development and structure and function study (Hanumantha et al, 2011). The expressions of recombinant polio and Dengue viral vaccines in P. pastoris have also been reported.…”

Section: Vlp Productionmentioning

confidence: 97%