Global Health Primer

What are Polysaccharide Protein Conjugate Vaccines?

Polysaccharide protein conjugate vaccines consist of polysaccharides, generally from the surface coat of bacteria, linked to protein carriers. The combination of the polysaccharide and protein carrier induces an immune response against bacteria displaying the polysaccharide contained within the vaccine on their surface, thus preventing disease.

Overview

Polysaccharide protein conjugate vaccines are primarily used for the prevention of bacterial infections. Some pathogenic bacteria are covered with a polysaccharide capsule that primarily helps protect the bacteria from phagocytosis, or uptake of the bacteria by immune cells. The production of specific antibodies to the polysaccharide coat in an infected person can increase phagocytosis of bacteria, thus stimulating an immune response. Therefore, vaccination using polysaccharides from pathogenic bacteria is a potential strategy for boosting host immunity.

The polysaccharides that cover bacteria vary greatly even within a single species of bacteria. For instance for Streptococcus pneumoniae, a bacterium that commonly causes pneumonia, there are more than 90 different serotypes due to variation in the bacterial polysaccharide coat. Therefore, polysaccharide vaccines often consist of a panel of polysaccharides to increase protection.

Although polysaccharides are immunogenic on their own, conjugation of polysaccharides to protein carriers has been used to improve immunogenicity. The carrier protein can be either a related protein antigen from the target pathogen, boosting the specific immune response to that pathogen, or a generally immunogenic protein that serves more as an adjuvant or general immune response stimulant.

Existing Products

As the application of polysaccharide protein conjugate vaccine technology is limited to a subset of bacteria, there are a limited number of polysaccharide protein conjugate vaccines currently in use. Examples of successful polysaccharide protein conjugate vaccines are listed here.

Vaccine Description Impact
Haemophilus influenzae B (Hib; bacterial meningitis and pneumonia) Hib is a major cause of meningitis in children <5 years old as well as a cause of pneumonia. The vaccines consist of polysaccharide linked to the tetanus or diphtheria toxoid proteins as carriers. The first Hib vaccine was approved by the FDA in 1985. As of 2009, the World Health Organization (WHO) estimates that global vaccination of children under 5 for Hib is 38%. Widespread use of the vaccine in the U.S. and western Europe has nearly eliminated Hib as a public health problem in infants.
Neissera meningitides (bacterial meningitis) Two vaccines are currently available for the prevention of meningitis caused by N. meningitides; MPSV4 has been available in the U.S. since the 1970s and MCV4 was FDA approved in 2005. The polysaccharides in MCV4 are conjugated to the diphtheria toxoid protein. The N. meningitides vaccines are primarily used in high risk populations in the developed world. A new meningitis vaccine developed jointly by WHO and PATH that is specifically designed to target meningitis in the 25 countries of the epidemic “Meningitis Belt” of sub-Saharan Africa was rolled out in 2010. The potential for impact of an N. meningitides vaccine in the developing world will largely be determined by the outcomes of this rollout.1
Streptococcus pneumoniae (bacterial pneumonia) There are current three vaccines in use for the prevention of S. pneumoniae, consisting of 10 and 23 polysaccharides conjugated to H. influenzae or diphtheria carrier proteins. S. pneumoniae vaccines are primarily used in high risk groups in developed countries such as the elderly. Because so many polysaccharides must be included to achieve immunity, these vaccines are too expensive for use in the developing world. The introduction of a US$1.5 billion Advance Market Commitment in 2009 aims to bring down the cost of pneumonia vaccines for use in the developing world which is likely to drive impact of these vaccines.

 

References

  1. WHO, MVP, and PATH joint press release, available here

 

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PIPELINE

Product/Research ProgramDevelopersDiscoveryPre-clinicalPhase IPhase IIPhase III
GSK2189242AGlaxoSmithKline
London School of Hygiene and Tropical Medicine
Medical Research Council, The Gambia Unit
PATH

 

 

 

 

V114Merck & Co., Inc.
Serum Institute of India Ltd.

 

 

 

 

Vi-CRM197Novartis Vaccines Institute for Global Health

 

 

 

 

GVXN SD133GlycoVaxyn

 

 

 

Shigella Sonnei O-SPC/rBRUEunice Kennedy Shriver National Institute of Child Health & Human Development

 

 

 

Shigella Sonnei OSPC-rDTEunice Kennedy Shriver National Institute of Child Health & Human Development

 

 

 

Carbohydrate-protein conjugate vaccinesKarolinska Institute

 

 

PmpD multivalent chlamydia vaccineNational Institute of Allergy and Infectious Diseases

 

 

Vi-DT conjugate vaccineInternational Vaccine Institute
National Institutes of Health
Shantha Biotech

 

 

Low-cost conjugate vaccine (PATH/CIBP)Chengdu Institute of Biological Products
PATH

 

Low-cost conjugate vaccine (PATH/SIIL)PATH
Serum Institute of India Ltd.

 

S. flexneri type 2a-rEPAsuccEunice Kennedy Shriver National Institute of Child Health & Human Development

 

 

 

 

On Hold

S. sonnei-rEPAEunice Kennedy Shriver National Institute of Child Health & Human Development

 

 

 

 

On Hold

Vi-rEPA Conjugate VaccineEunice Kennedy Shriver National Institute of Child Health & Human Development

 

 

 

On Hold

OmpC-Vi conjugate vaccineAll India Institute of Medical Sciences

 

On Hold

ANALYSIS

New polysaccharide protein conjugate vaccines focus on improving upon existing pneumococcal vaccines and the development of new shigellosis vaccines. The overall strengths and weaknesses for this approach are summarized here.

Strengths Weaknesses
Immune response to polysaccharides from bacterial surface is well characterized and known to be protective Primarily limited to production of humoral immune response which is not generally sufficient for intracellular infections
Clear regulatory pathway Application primarily limited to bacterial infections
Conjugation to protein carries acts as adjuvant Generally provides protection to narrow range of serotypes; adding additional serotypes increases cost

 

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 or contact us at globalhealthprimer@bvgh.org.

 Databases/Resources

Polysaccharides protein conjugate vaccines benefit from advances in understanding of bacterial polysaccharides and glycobiology. Several online resources exist detailing the biology of these macromolecules, including:1,2,3

More information on the availability of tools for vaccine development for specific neglected tropical diseases is available in each of the specific disease profiles.

References

  1. Esko JD (ed.) Chapter 21: Bacterial Polysaccharides in Essentials of Glycobiology, 1999. Available here.
  2. Marchal I et al. (2003) “Bioinformatics in Glycobiology.” Biochemie 85: 75-81.
  3. Von der Lieth CW et a. (2004) "Bioinformatics for glycomics:  status, methods, requirements and perspectives." Briefings in Bioinformatics 5: 164-178.

 

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 or contact us at globalhealthprimer@bvgh.org.

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