Immunogens, subunit vaccines

Brynestad K, et al. Influence of peptide acylation, liposome incorporation, and synthetic immunomodulators on the immunogenicity of a 1-23 peptide of glycoprotein D of herpes simplex virus implications for subunit vaccines. J Virol 1990 64 680. 

Subunit vaccines Immunogenic proteins or peptide antigens customized to specific antigenic determinants are purified from tissue culture HIV, rabies virus, influenza virus, hepatitis B virus... 

Alvarez, M.L., Pinyerd, H.L, Crisantes, J.D., Rigano, M.M., Pinkhasov, J., Walmsley, A.M., Mason, H.S., and Cardineau, G.A. (2005). Plant-made subunit vaccine against pneumonic and bubonic plague is orally immunogenic in mice. Vaccine 24(14) 2477-2490. 

Although there are a number of advantages associated with the use of subunit vaccines (e.g., highly purified peptides, proteins or DNA) as vaccines (e.g., specificity), one feature they all have in common is that they are generally poorly immunogenic. The more traditional vaccines contain many other components, some of which elicit additional T-cell assistance or function as adjuvants. An adjuvant is a substance that acts as an immunostimulator, one example being the bacterial DNA in a whole cell vaccine. The overall result is a more robust immune response than that provided by the antigen alone. 

Bacterial toxins such as diphtheria and tetanus can damage host cells but the isolated toxins can also be immunogenic. However, the induced response may not always be very strong and booster shots are required every 10 years. Adjuvants could improve the response and both diphtheria and tetanus toxoids are more effective when combined with pertussis subunit vaccines, the DPT combination at present used clinically. 

A subunit vaccine consists of one or more immunogenic epitopes, proteins, or other components of a pathogenic organism. Immunogenic epitopes can be chemically synthesized and are known as peptide vaccines, e.g., peptide vaccine candidates for foot-and-mouth disease virus. The pathogen could be disrupted, and one or more immunogenic proteins such as bacterial cell wall proteins flagella or pili and viral envelope, capsid, or nucleoproteins can be purified. The isolation of such components in purified form is sometimes cumbersome and expensive. However, bacterial exotoxins can be easily purified, inactivated, and used as toxoid vaccines. 

Ruf BR, Colberg K, Frick M, Preusche A (2004) Open, randomized study to compare the immunogenicity and reactogenicity of an influenza split vaccine with an MF59-adjuvanted subunit vaccine and a virosome-based subunit vaccine in elderly. Infection 32 191-198... 

In addition, the adjuvant should be a stable component and it should not be immunogenic by itself In traditional vaccines very often components of organisms acted as adjuvants, and/or aluminum salts were used. With the need to develop novel subunit vaccines, it quickly emerged that novel and more effective adjuvants were also needed. 

Recently, several live attenuated and subunit vaccine candidates have been constructed using an RSV infectious clone. However, striking a balance between immunogenicity and attenuation has proved to be difficult, since any augmentation of attenuation usually results in decreased immunogenicity. Two s... 

Influenza. Although current influenza vaccine (subunit spHt vaccine) has been in use yearly for the elderly, it is not recommended for the general population or infants. Improvements to increase or prolong the immunogenicity, reduce the side-effects (due to egg production procedure), and provide mass protection are stiU being pursued. One approach is to use a five, attenuated vims though cold adaptation. A vaccine has been used in Russia and demonstrated to be safe and efficacious for infants (82). Clinical trials for a similar vaccine are being carried out in the United States (83). 

Moravec, T., Schmidt, M.A., Herman, E.M., and Woodford-Thomas, T. (2007). Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine. Vaccine 25(9) 1647-1657. 

Rigano, M.M., Dreitz, S., Kipnis, A.-R, Izzo, A.A., and Walmsley, A.M. (2005). Oral immunogenicity of a plant-made subunit tuberculosis vaccine. Vaccine 24(5) 691-695. 

Cataldo DM, Van Nest G. The adjuvant MF59 increases the immunogenicity and protective efficacy of subunit influenza vaccine in mice. Vaccine 1997 15 1710-1715. 

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