See “ways to increase immunogenicity” on outline

See WHO   See History of Vaccines 

Active immunization refers to stimulation of an immune response by challenge with an immunogen. Active immunization occurs after each exposure to an infectious agent (natural immunization) and through exposure to antigens in vaccines. 

Attenuated Viruses :

Companies: Codagenix  Emergex vaccines

Attenuated viruses (i.e., less virulent) pathogens or closely related organisms, was first demonstrated by Edward Jenner in 1796, who vaccinated against smallpox by the administration of a less dangerous cowpox virus. Although a number of live attenuated viruses (e.g., measles, mumps, rubella, varicella, adenovirus, polio, influenza) and bacterial (e.g., bacille Calmette-Guerin (BCG) against tuberculosis) are sucessfully administered for vaccination, there is a risk for the development of serious complications related to a reversion to virulence and infection by the “vaccine” organism, in particular in immunocompromised individuals. The specific design of attenuated viruses is now enabled by recombinant DNA technology through the generation of deletion or mutation variants. unlike isolated proteins, viruses induce prompt and efficient immune responses in the absence of adjuvants. 

Some believe that live, attenuated vacines could play a larger role against many infections, particulalry respiratory infections. While it is clear with some of the mRNA vaccines one gets a good antibody response, it is realtively sort lived. In the influenza setting, one sees most of the infections limited to the winter. This does not seem to be the case with COVID-19 where one sees increases in late spring and early summer. Promoting booster vaccines int he ealry fall if you have lsot most of your immunity covrerage by January or Febraury does not help if you get potentially exposed in the late spring and early summer. 

Components of a pathogen: 

Using components of a pathogen is an alternative approach for vaccination. Isolated components of a pathogen either purified form the pathogen or after expression of a single viral protein (e.g., hepatitis B surface antigen) are administered to induce neutralizing antibodies. Examples include influenza hemagglutinin or neuroaminidase. In the HIV front, recombinant proteins of HIV (gp120 and full lenght gp160) have been evaluated as a means to induce neutralizing antibodies against HIV but with disappointing results. It is well established that the administration of purified proteins is not usually not sufficent to elicit a strong immune response but generally must be given together with helper substances called adjuvants.  

DNA vaccines: (See outline)

Fusion Proteins  (see also drug delivery)

Elastin-like Peptides (ELP) fusions: (Floss, J. Biomedicine and Biotechnology, 2010, article ID 27434) discloses a fusion between elastin-like peptide (ELP) and Ag85B and ESAT-6 which are produced in plants. Mice and piglets immunized with the TBAg-ELP fusion exhibited exhibited a mycobacterial specific immune response with no side effects. The main reactivity of the TBAg-ELP induced antibodies against Ag85B. 

Virus like particles (VLPs):

Companies: Osivax

VLPs are being exploited as vaccines because of both their structural properties and their non-infectious nature. VLPs are supermolecular structures built in a symmetrix manner form many protein molecules of one or more types. Because they lack the viral genome, they are noninfectious. Examples include the capsid proteins of HBV, measles virus, Sindbis virus, rotavirus (US 5071651 and 5374426), foot and mouth disease virus, the retroviral GAG protein (WE 96/30523), the retrotransposon Ty protein p1, the surface protein of HBV (WO 92/11291) and human papilloma virus (WO 98/15631). Renner (WO 00/32227) discloses a (i) molecular scaffold and an (ii) antigen or antigenic determinant. The (i) moelcular scaffold comprises a core particle such as a VLP, a bacteriophage or a virus and at least one attachment site connected to the core particle by at least one covalent bond. The (ii) antigen or antigenic determinant has at least one second attachment site which can associate with the first attachment site to form an ordered and repetitive antigen.  

To date, VLPs have been produced for more than 30 different viruses that infect humans and other animals. One of the most striking features of this group is that it is extremely diverse in terms of the structure of the individual viruses. (Noad, “Virus-like particles as immunogens” Trends in Microbiology, 11(9), 438-444, 2003).