What is Recombinant or Purified Protein Vaccines?

Recombinant or purified protein vaccines consist of protein antigens that have either been produced in a heterologous expression system (e.g., bacteria or yeast) or purified from large amounts of the pathogenic organism. The vaccinated person produces antibodies to the protein antigen, thus protecting him/her from disease.

Overview

Recombinant/purified protein vaccines are based on the concept that humoral immune responses mounted to an infection are often targeted toward specific localized regions on the surface of protein antigens known as epitopes. The recombinant proteins for vaccination are produced by expressing these immunogenic proteins using heterologous expression systems. The immunogenic protein antigens can also be purified from the infectious organism. Once purified, protein antigens, recombinant and endogenous, are administered with an adjuvant to boost the immune response. Administering just the most immunogenic protein or proteins from an infectious organisms as a vaccine produces a more targeted immune response. This strategy also eliminates the risk of active infection that can occur with live attenuated vaccines or even inactivated vaccines where inactivation is incomplete.

Existing Products

There are a limited number of recombinant/purified protein vaccines currently in use. Examples of successful recombinant/purified protein vaccines are listed here. The majority of on market vaccines using this strategy are related to protecting a person against the damage caused by secreted toxins rather than protecting a person against infection by the bacterium or virus.

Vaccine Description Impact
Cholera Recombinant cholera toxin B is a component of Dukoral, a cholera vaccine that also contains inactivated whole bacteria. Dukoral has limited efficacy and duration of immune response. Interestingly, Dukoral provides some cross protection against enterotoxigenic E. coli (ETEC) due to similarities between ETEC and cholera toxins. Cholera vaccines are not yet widely available, so the true impact of these vaccines has not been determined.
Diphtheria Diphtheria vaccine is based on purified diphtheria toxin that is chemically inactivated. The inactivated toxin is referred to as a toxoid. As it is the toxin rather than the bacterium that causes the majority of diphtheria symptoms, producing antibodies to the toxin protects against symptomatic disease even though it does not prevent infection with the bacteria. Since the introduction of the combined diphtheria, tetanus, pertussis vaccine through the World Health Organization (WHO) Expanded Program on Immunization in 1974, reported diphtheria cases dropped by more than 90%.
Hepatitis B A recombinant protein vaccine against hepatitis B infection has been available since 1981. The vaccine uses hepatitis B surface antigen produced in yeast. The number of countries providing hepatitis B vaccinations has increased from 31 in 1992 to 164 in 2006. As the health impact of hepatitis B is associated with chronic infection, the health impact of the vaccination has not been extensively measured.
Tetanus Similar to the diphtheria vaccine, the tetanus vaccine is based on the use of inactivated tetanus toxin to produce antibodies that neutralize the toxin even though they do not kill the infectious bacteria. As mentioned above, the combined diphtheria, tetanus, pertussis vaccine has had a significant health impact. The focus of tetanus vaccination is on the prevention of mother to neonatal transmission of the bacteria that cause tetanus.

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Pipline

Analysis

Although there are a limited number of recombinant or purified protein vaccines currently in use, recombinant protein vaccines make up the majority of products in development for neglected tropical diseases. The overall strengths and weaknesses for viral, bacterial, and parasitic diseases are summarized here.

Strengths Weaknesses
Long history of successful use for a variety of infectious diseases Protein purification and correct folding can be challenging
Clear regulatory pathway Limited to primarily humoral immune response

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To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs.

Recombinant and purified protein vaccines benefit from extensive resources from the biochemistry community for the production and purification of proteins including:

  • Multiple heterologous recombinant protein expression systems (e.g., bacteria, yeast, mammalian cells, cell free extracts)
  • Multiple protein tagging and purification methods (e.g., epitope tags, affinity tags, cleavable tags)
  • Automated protein purification systems (e.g., variety of fast protein liquid chromatography systems using gel filtration, anion/cation exchange, or hydrophobic properties

There are numerous publications and manuals with detailed protocols for protein expression and purification especially from vendors who sell protein purification equipment and accessories.1-3

More information on the availability of tools for protein antigen identification and expression for specific neglected diseases is available in each of the specific disease profiles.

References

  1. Walker JM (ed.) The Protein Protocols Handbook, 3rd edition, 2009.
  2. Promega Protocols & Applications Guide: Protein purification and analysis, available here.
  3. Elsevier scientific journal: Protein Expression and Purification,  available here.

Get Involved

To learn how you can get involved in neglected disease drug, vaccine or diagnostic research and development, or to provide updates, changes, or corrections to the Global Health Primer website, please view our FAQs.