Future of vaccines

One cannot think about the future of vaccines in the 21st century without taking a look at the past. In fact, thanks to the pioneers of vaccination and to a handful of vaccines, obtained and applied using "hybrid" methods, in part empirical and in part scientific, the world has witnessed a striking reduction in infectious diseases.

The global eradication of smallpox is the poster-child of this achievement. If we look to the very recent past and the present, we can see that in the last ten years many important vaccines have come into being, including the monovalent C meningococcal conjugate vaccine , the tetravalent meningitis ACYW-135 conjugate vaccine, the heptavalent and the 13-valent conjugate for S. pneumoniae infections and the cervical carcinoma vaccine. Nevertheless, many problems remain unresolved such as the emergence or re-emergence of new infectious diseases at the turn of the 21st century, namely AIDS, SARS, the 2009/10 pandemic flu, cholera, dengue, tuberculosis, etc.1.

At the same time it is worth remembering that vaccines are helping to combat some important degenerative diseases, such as cervical cancer. The hope we place in vaccinations to improve the health of populations is based on the continuous progress of sciences such as immunology. In fact, the increasing understanding of the functioning of immune system, for example the best definition of the relationships between cells in order to understand how they communicate with each other, their role, the importance of soluble mediators (lymphokines, complement, antibacterial proteins, etc), the identification and definition of the role of cellular receptors (toll-like receptors), etc., already enables us to make breakthroughs in the development of new vaccines. However, many issues still need to be resolved. These are caused by the vital need of pathogenic microorganisms to resist the natural or artificial defences that our body can erect, often by bypassing them. Thus, like the more phylogenetically-evolved organisms, they are able, albeit in a different way, to guarantee species variability. The influenza virus offers a prime example of this ability: it is capable of implementing minor variations in accordance with seasonal flu epidemics, and major variations which can cause pandemics. Another important example is meningococcus, which presents a large range of capsular antigens and a strong ability to vary surface antigens, such as lipopolysaccharides (Lps). In these last two cases, research has progressed impressively, leading to both the construction of artificial viruses, ideal for the preparation of new vaccines, and to a "reverse vaccinology" approach (a combination of molecular and computer biology techniques), enabling the development of the meningitis B vaccine and offering preventive vaccination prospects for other pathogens such as group B and group A streptococcus, streptococcus pneumoniae and antibiotic-resistant staphylococcus aureus2.

Furthermore, while to date the methods used to measure the immune response to vaccines have been developed in order to administer antibodies in the correct doses, in the future the evaluation of cell-mediated immunity will be increasingly used, thanks to new laboratory methods such as: Eelispot (which enables counting the cells that produce); the measurement of the intracellular interleukins (Iccs); and the possibility of studying the role of the single antigenic epitopes on the cell-mediated response. At the same time, other important aspects of modern vaccinology are worth highlighting, namely: the use of new substances to enhance the vaccines’ abilility to trigger an immune response (such as water oil mixtures [MF-59] or AS04 [monophosphorylipide A]), the increasingly necessary development of combined vaccines for routine vaccination (e.g. the hexavalent vaccines used in Europe and the pentavalent vaccines in many other countries around the world); the possible extension of the application of vaccines with the prospect of therapeutic vaccines (e.g. considering the studies on the oncogenes E6 and E7 of the papillomavirus and research into the functional genes of the gag and tat of HIV to suppress the replication of the AIDS virus); the use of new methods for the administration of vaccines (for example the administration by aerosol for the influenza and measles vaccines; oral administration through transgenic foods, rectal or vaginal administration, or transdermal administration by means of appropriate inoculation systems); the opportunity to vaccinate new categories of target subjects (adolescents [Hpv, pertussis, meningococcus, cytomegalovirus, genital herpes], adults [flu, pneumococcal vaccines, varicella], pregnant women [vaccines for group B streptococcus, pneumococcus, influenza, etc. ], travellers, subjects requiring hospitalisation [a vaccine for staphylococcal and candida infections], the elderly [tetanus, influenza, pneumococcal vaccines and herpes zoster vaccines] are being developed.

It is worth reiterating that vaccines will increasingly constitute an important weapon in cancer prevention. In particular, the vaccine for papillomaviruses is an example that can also be followed for other neoplasms. Even before the HPV vaccine had been developed, a DNA-recombinant vaccine against hepatic carcinoma existed, and it is hoped, with the development of a vaccine against Helicobacter pylori, that there will soon be an important weapon in the fight against stomach cancer. Finally, Kaposi's sarcoma may also be prevented with the development of a vaccine against AIDS and/or herpes simplex8.

It is hoped that vaccines may be developed for other diseases, such as Parkinson's and diabetes.

Nossal has divided the vaccines of the future into three groups: those that will be available in the near future (within ten years), namely the conjugate vaccine for typhus and the vaccine for meningitis B while slightly later, vaccines for shigella infection and a universal vaccine for pneumococcal infections should be available; malaria, tuberculosis and AIDS vaccines, should be available within 10 to 19 years; and others, such as autoimmune vaccines, juvenile diabetes, and celiac disease, according to Nossal, should be available within a timeframe ranging from 20-50 years3.

It is equally interesting to consider that the abundant acquisition of cutting-edge knowledge and the opportunity of a "cross-scientific approach" will create further possibilities for improvement, not only for the development of new vaccines, but also for their optimal use. Thus, as of now, the application of Health Technology Assessment (HTA, syncretic evaluation of the evidence regarding the efficacy and safety of vaccines, of the results of health economics studies, of ethical, social and political aspects) in the field of preventive vaccination is being developed. This implies that the future holds old and new challenges in store: educating the population on the right health choices; counteracting the various movements which, despite lacking any scientific logic, oppose vaccination; and helping decision-makers to best solve such complex health problems as those relating to vaccinations4.

Sources / Bibliography
  1. Gasparini R, FrancoE . NUOVI VACCINI, NUOVI VACCINI PER L'INFLUENZA PANDEMICA (ultimo 01/04/2013)
  2. Sette A, Rappuoli R. Reverse Vaccinology: Developing Vaccines in the Era of Genomics. Immunity 2010; 29; 33(4): 530-541
  3. Nossal GJV. Vaccines of the future. Vaccine 2011; 29S: D111-D115
  4. Ricciardi W, Bamfi F. Descrizione dell’HTA e inquadramento metodologico del progetto sul vaccino anti-pneumococcico coniugato con la proteina D dell’ Haemophilus influeanzae non tipizzabile Synflorix™ (PHiD-CV). Italian Journal of Public Health 2009, 6 Suppl 5:S1-S4
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