Vaccines stimulate the body's immune system to prevent or control specific diseases. Vaccines against major human infectious
diseases such as pertussis, diphtheria, tetanus, and tuberculosis were developed in the early 1900s, and those for polio,
mumps, measles, and rubella were not licensed until the 1960s. Because of the widespread use and effectiveness of antibiotics,
and the low profit margins and liabilities associated with vaccine products, interest in vaccines diminished in the 1980s
and early 1990s. The recent renaissance in vaccines is fueled by multiple factors. New developments in modern biotechnology
and immunology have made it possible to produce novel antigens and create new vaccine technologies. The recent licensures
of high-profile vaccine products not only offered major contributions to human health but also achieved significant commercial
success for the developers. These include Prevnar, a pneumococcal glycoconjugate vaccine; Gardasil, a human papilloma virus
(HPV) vaccine; Rotarix and Rotateq, rotavirus vaccines; and Zostavax, the herpes zoster vaccine. Other factors include concerns
over possible pandemic flu outbreaks and bioterrorism, the emergence of antibiotic-resistant pathogens, and increased funding
from both private and public sectors. The current vaccine market is estimated at about $10 billion worldwide and is expected
to double in the next five years.
Table 1. Vaccines licensed in the US
Vaccines currently licensed in the US are listed in Table 1.1 Vaccines can be divided into four broad categories: live attenuated vaccines, inactivated vaccines, subunit vaccines, and
conjugated vaccines. Live vaccines are usually weakened viruses or bacteria that are no longer capable of causing diseases
but can still stimulate immune response in the hosts. Good examples are MMR II, Flumist, and Rotateq. Inactivated vaccines
are composed of killed virus or bacteria, such as the polio virus vaccine and the rabies vaccine. Subunit vaccines are made
from one or more components of a microorganism. Examples are the Streptococcus pneumoniae polysaccharides vaccines and the recombinant Hepatitis B vaccines. Conjugated vaccines are prepared by conjugating a subunit
to a carrier protein or other immuno-stimulating agents. An example is Prevnar (7-valent capsular polysaccharides of S. pneumoniae conjugated to a carrier protein CRM197).
NEW VACCINE TECHNOLOGIES
Table 2. New vaccine technologies
Significant efforts have been undertaken to identify and develop new vaccine technologies (Table 2).2–3 Inactivated pathogens, recombinant proteins or peptides (with or without adjuvants) are inefficient in inducing T-cell response.
Plasmid DNA-based vaccines elicit strong antibody and T-cell responses in animals. Attempts to enhance immune responses to
DNA vaccines in humans have been made using new formulations with cationic lipids, electroporation, or the incorporation of
cytokine genes in the construction, with promising results. Viral–vector based vaccines tested in humans include attenuated
pox viruses (vaccinia or avipox viruses) or adenovirus. Lipopeptides, presenting peptide antigens in association with a lipid
moiety, have also been synthesized and tested as candidate vaccines against HBV, HPV, and HIV-1 infections to induce T-cell
responses. Transgenic plants, expressing antigens from various pathogens, have been evaluated for vaccination through the
oral route, and generated encouraging results when tested in animals. Monocyte-derived dendritic cells, loaded with antigens
(presented as peptides, proteins, RNA or recombinant viruses), have generated good results in cancer patients.
No single vector alone can elicit optimal immune responses in humans. Thus, there is a trend to use multiple vectors as part
of mixed immunization regimens. In such heterologous prime–boost vaccination schemes, the antigen is presented to the immune
system using a "priming" vector. A second vector is used as a booster to present the very same antigen. Collectively, such
mixed immunization regimens have been shown to elicit stronger antibody, T-cell, and cytotoxic T lymphocyte responses. Association
between DNA and pox viruses or vaccinia and canarypox appears to be particularly promising in inducing effective immune responses.