A vaccine against pertussis containing purified proteins was first created in 1981 in Japan by Sato and Sato, who purified the antigenic proteins by classical biochemical methods from cultures of the pathogen —with the obvious problems in biological safety and with upscaling of the procedure [ 1 ]. Another example is the hepatitis B vaccine which contains one of the proteins from the viral envelope—the hepatitis B surface antigen (HBsAg). This was one of the first protein-based vaccines, and while at first the protein was obtained from natural human plasma, it was later successfully expressed recombinantly in yeast cells. Today, this is the production method of choice for human vaccines [ 2 ]. Another example of a subunit vaccine on the market is the one against Bacillus anthracis . Although the components are still collected from pathogen cultures, which raises concerns about the safety of the procedure, the strength of the initial immune response and long-term efficacy are high [ 3 ].

Some studies have included production of plasmid-derived antigens using attenuated, avirulent Bacillus strains. Expressing these proteins in a Bacillus strain ensures properly processed and folded protein. The product is then purified from fermentation cultures and adsorbed onto an aluminum adjuvant . Preclinical studies showed that the vaccine as such is safe and well-tolerated and can induce an immune reaction with long-term immunity. Researchers are also looking for new targets using bioinformatics, now that the complete genome of the clinical strain is available [ 4 , 5 ].

Two new vaccines against human papillomavirus (HPV) have been brought to the market recently—Cervarix and Gardasil (Silgard). Both contain proteins from the capsids of different virus strains—HPV16 and 18 and HPV6, 11, 16, and 18, respectively— and differ in the formulation of enhancers and adjuvants. In 2014, the US Food and Drug Administration approved another new HPV vaccine from Merck, Gardasil 9, which protects against 9 subtypes of the virus (HPV6, 11, 16, 18, 31, 33, 45, 52, and 58). These vaccines are all produced recombinantly using yeast cells (or insect cells for Cervarix) [ 6 – 7 ].

In ongoing Phase III clinical trials, promising results have been obtained for a vaccine against Pseudomonas aeruginosa (IC43). This is an outer membrane protein-based vaccine containing an OprF/OprI fusion with a His tag. The product is expressed in E. coli from a plasmid. The vaccine gives good immune response s with and without an aluminum adjuvant [ 8 , 9 ] (Table 1 ).

Table1. Advantages of protein-based vaccines [ 10 , 11 ]

References

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[1] Sato Y, Sato H (1999) Development of acellular pertussis vaccines. Biologicals 27:61–69

[2] Michel M-L, Tiollais P (2010) Hepatitis B vaccines: protective efficacy and therapeutic potential. Pathol Biol 58:288–295

[3] Cybulski RJ, Sanz P, O’Brien AD (2009) Anthrax vaccination strategies. Mol Aspects Med 30:490–502

[4] Chun JH, Hong KJ, Cha SH et al (2012) Complete genome sequence of Bacillus anthracis H9401, an isolate from a Korean patient with anthrax. J Bacteriol 194:4116–4117

 [5] Keitel WA (2006) Recombinant protective antigen 102 (rPA102): profile of a second- generation anthrax vaccine. Expert Rev Vaccines 5:417–430

 [6] McKee SJ, Bergot A-S, Leggatt GR (2015) Recent progress in vaccination against human papillomavirus-mediated cervical cancer. Rev Med Virol 25:54–71

 [7] Merck. http://www.merck.com

 [8] Vincent J-L (2014) Vaccine development and passive immunization for Pseudomonas aeruginosa in critically ill patients: a clinical update. Future Microbiol 9:457–463

[9] Westritschnig K, Hochreiter R, Wallner G et al (2014) A randomized, placebo- controlled phase I study assessing the safety and immunogenicity of a Pseudomonas aeruginosa hybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers. Hum Vaccin Immunother 10:170–183

[10] Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6:404–414

 [11] Skwarczynski M, Toth I (2014) Recent advances in peptide-based subunit nano vaccines. Nanomedicine 9:2657–2669

مواضيع ذات صلة

Microbiota, Chronic Infections, and Vaccines

Vaccines and the Role of Pre-existing Immunity

Methods for Using Full-Length Antigens (Proteins) as Vaccines

Pan-Genomic Analysis

Reverse Vaccinology

Improving Vaccines over Natural Immune Responses

Selecting Vaccine Antigens

Principles of Vaccine Development

A Brief History of Vaccination

Development of Vaccines for Tuberculosis and Meningitis

Development of Vaccines for Viral Hepatitis, Coronavirus, and Norovirus

Development of Powerful Influenza Vaccines