Vaccine, Subunit

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). 

Vector-Based Vaccines Viruses and bacteria are detoxihed and used as vehicles to carry vaccines. Subunit vaccines are delivered by carrier vehicles to elicit the immune response. An example is the use of canarypox (a virus that infects birds, but not humans) to carry envelope proteins for HIV treatment. Multiple types of envelope proteins can be delivered with this method. Clinical trials with this type of vector-based vaccines are being investigated. 

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

Rotavirus. Rotavims causes infant diarrhea, a disease which has major socio-economic impact. In developing countries it is the major cause of death in infants worldwide, causing up to 870,000 deaths per year. In the United States, diarrhea is stiU a primary cause of physician visits and hospitalization, although the mortaUty rate is relatively low. Studies have estimated a substantial cost benefit for a vaccination program in the United States (67—69). Two membrane proteins (VP4 and VP7) of the vims have been identified as protective epitopes and most vaccine development programs are based on these two proteins as antigens. Both Hve attenuated vaccines and subunit vaccines are being developed (68). 

Vaccine candidates are based on the two viral surface proteins, gD and gB (80). Recombinant methods are used to express the proteins, either in Chinese hamster ovary (CHO) cells or in baculovims. The proteins are purified as subunits and formulated with different adjuvants. Clinical trials with these vaccine candidates have been performed, but the results to date have not been encouraging. 

Subunit vaccines based on the surface proteins of vims are also being explored. It has been demonstrated that the two major protective antigens are haemagglutinin (HA) and neuraminidase (NA). The genes for these antigens have been cloned and expressed in baculovims in insect cell culture (84). 

The basic process technology in vaccine production consists of fermentation for the production of antigen, purification of antigen, and formulation of the final vaccine. In bacterial fermentation, technology is weU estabHshed. For viral vaccines, ceU culture is the standard procedure. Different variations of ceU line and process system are in use. For most of the Hve viral vaccine and other subunit vaccines, production is by direct infection of a ceU substrate with the vims. 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

R. Eby, in M. PoweU and M. Newman, eds.. Vaccine Design The Subunit and Adjuvant Approach, Plenum Press, New York, 1995, Chapt. 31. 

Research on an hCG vaccine has been conducted over the past 15 years. WHO has conducted a phase I clinical study in AustraUa, using a vaccine based on a synthetic C-terminal peptide (109—141) of P-hCG conjugated to Diptheria Toxoid (CTP-DT), that showed potentially effective contraceptive levels of antibodies were produced in vaccinated women without any adverse side effects. Phase II clinical studies are under consideration to determine if the immune response, raised to its prototype anti-hCG vaccine, is capable of preventing pregnancy in fertile women volunteers (115). While research on the C-terminal peptide from the P-subunit of hCG has been carried out under the auspices of WHO, research supported by the Population Council and the National Institutes of Health has involved two alternative vaccine candidates (109,116,118). 

Payne LG, Jenkins SA, Andrianov A, Roberts BE (1995) In PoweU MF, Newman MJ (eds) Vaccine design The subunit and adjuvant approach. Plenum, New York, USA, chap 20, p473... 

To identify and characterize bacterial and viral antigens which can then be purified and used to prepare subunit vaccines. 

Classify each of the routine vaccines as an inactivated, polysaccharide, conjugate, toxoid, or subunit vaccine. 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

Black M, Trent A, Tirrell M et al (2010) Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines 9 157-173... 

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