The History And Importance Of Vaccines In Strengthening The Human Immune System

Vaccination – History, Discovery, Configuration, Extraction, Development, and Immune System Improvement

Vaccination effectively helps in facilitating the body’s immune mechanism to defend against a range of debilitating disease conditions. Vaccines are prepared after a substantial modification of natural immunogens comprising of toxins or pathogens. Vaccination activates the responses of naïve T and B cells that resultantly induce the targeted antibodies and memory cells¹. The antibodies target the corresponding pathogen and memory cells effectively record the antigen-antibody binding pattern for an extended tenure. The subsequent attack of the same pathogen induces a secondary response of the same antibodies that completely eradicate the pathogen invasion from the human body. The discovery of the following significant vaccine between 18-21 century revolutionized the prophylaxis and prevention of various debilitating disease conditions.      

The discovery of the first vaccine (i.e. smallpox) occurred 300 years ago in year². Edward Jenner discovered that the milkmen affected with cowpox virus never acquired a smallpox infection in their lifetime. Eventually, the information regarding the attenuation of cowpox virus in the human body assisted Edward Jenner to utilize this vaccine for challenging the smallpox outbreak. The development of the smallpox vaccine helped the researchers to initiate further studies for determining the cross-protection properties of poxvirus isolates³. The second-generation smallpox vaccine is prepared from the primary kidney cells of the rabbit. However, the third-generation smallpox vaccines were never evaluated across the endemic settings. The replication competent LC16m8 vaccine was extracted from the kidney cells of rabbit at a temperature of 30 degrees Celsius. The administration of smallpox vaccine effectively improves the cellular immune responses against the viral invasion. The individuals with T-cell deficiency also benefit from the smallpox vaccine while acquiring an extended protection from the smallpox virus for a period of 3-10 years⁴.

However, the vaccine for rabies was developed by Louis Pasteur in the year 1885. This vaccine was initially used to treat the victim of the human bite. Rabies vaccine was discovered when Pasteur injected an attenuated or weak virus from a rabid dog to another animal. The injection protected the animal from a rabid infestation. Following the same theme, the inactivated homogenate of the spinal cord of RABV (rabies virus) infected rabbit was extracted in the dried form and subcutaneously injected into the intended patient for establishing protection against rabies. Subsequently, the injection of partially active/virulent viral preparation was administered to obtain the therapeutic outcomes⁵. Eventually, WHO approved the pre-exposure and post-exposure rabies vaccination (through intramuscular injection) to challenge the risk of Lyssavirus infection before and after the occurrence of an animal bite/contact. FDA has approved three types of rabies vaccines including HDCV (Human Diploid Cell Vaccine), DCO (Inactivated Diploid Cell Origin), and MBPI (Michigan Biologic Products Institute)⁶. Rabies vaccine effectively induces the antibody that neutralizes the rabies virus and enhances the protective immunity of the individual affected with the animal bite. The preparation of the rabies vaccine is entirely based on cell culture technique. For example, Verorab is a rabies vaccine extracted from the cells of African Green Monkeys using cell culture technique⁷.

The tetanus etiology was tracked by Rattone and Carle when they subcutaneously inoculated the human tetanus pus cells into various healthy animals⁸. The passive immunization against C. tetani was developed by Nocard during the year 1897. The passive antitoxin helped in controlling the development of tetanus in the individuals who were initially exposed to C. tetani. However, Ramon utilized formaldehyde to prepare a deactivated toxin for tetanus prevention in the year 1920. Descombey in the year 1924 performed further research on the same deactivated toxin and configured a tetanus toxoid for treating tetanus affected/exposed patients⁸. The tetanus antitoxin is delivered intramuscularly to the intended recipients in the context of controlling the tetanus toxicity. However, the intravenous immune globulin effectively deactivates the tetanus toxin across the body tissues as well as the nerve endings. The different types of tetanus vaccines include the tetanus toxoid (TT), acellular pertussis, whole-cell, low-dose diphtheria toxoid, and diphtheria toxoid vaccines. DTaP and DTwP vaccines are recommended in five dosages for children and adolescents of various age groups⁹. The immunization through tetanus toxoid against neonatal tetanus significantly decreases the rate of neonatal morbidity and mortality¹⁰.   

Small Pox Vaccine

The injectable form of the polio vaccine was developed in the year 1955; however, the oral polio vaccine was developed in the year 1963 for preventing the onset and establishment of polio disease. Dr. John Enders performed several experiments to evaluate the scope of poliovirus culture across the human cell lines. The development of the polio vaccine was the outcomes of the research interventions by Sabin and Salk who undertook numerous preclinical studies for developing the polio vaccine¹¹. Albert Sabin utilized in-vitro cell culture passage for clones’ selection in the context of configuring the oral polio vaccine. The selected clones exhibited limited neurovirulence and incapacity to cause paralysis in the intended recipients. These clones experienced several mutations across the human intestine after their oral ingestion 2. This substantially reduced the risk of vaccination-based paralysis in the human population. The oral polio vaccine is based on the poliovirus (attenuated) strains obtained from the distinct serotypes. The vaccine strains effectively comply with the human immune response and rarely invade the central nervous system (CNS). The oral polio vaccine assists in providing serum and humoral immunity against poliovirus. The timely administration of oral polio vaccine barricades the transmission of the poliovirus types across the CNS¹². The oral poliovirus also facilitates the induction of local immune reaction across the intestinal mucosa to effectively challenge the replication of the debilitating poliovirus. The antibodies induced by the oral polio vaccine cease the spontaneous replication of the wild types of poliovirus.      

Acellular pertussis vaccine (APV) was developed in the year 1996 in the context of overcoming the whole-cell pertussis vaccines. The characterization and isolation of Bordetella pertussis antigens were performed in the year 1974 by Sato and Sato¹³. This substantially assisted the development of acellular pertussis vaccine that comprised of filamentous haemagglutinin and pertussis toxin. The utilization of the acellular pertussis vaccine has assisted in the radical elimination of pertussis from several parts of the world, including Japan. The acellular pertussis vaccine is rarely associated with significant adverse reactions and used as an integral element of multivalent DTP combination vaccine¹⁴. The several antigens in the acellular pertussis vaccine potentially protect against the deleterious effects of Bordetella pertussis and exhibit limited sensitivity against the protective immunity deterioration. The administration of the acellular pertussis vaccine substantially activates the immune protection responses of Th2 and Th1 in the human body¹⁵. The preparation of acellular pertussis vaccine is based on hydroxylapatite chromatography warranted for generating 68% and 62% purified form of filamentous hemagglutinin (FHA) and pertussis toxin (PT). The addition of hydroxylapatite helps in improving the antigen concentration while concomitantly minimizing the percentage of contaminants. The combined purity level of FHA and PT facilitates the native protein recovery to a considerable extent. The extraction of APV’s antigenic elements is based on the sequential detoxification of FHA and PT through the utilization of formaldehyde and glutaraldehyde¹⁶.

Conclusion

A thorough assessment of the history, discovery process, development, and methodology of human vaccines is necessarily warranted to evaluate the level of immune system responses and eventual prevention of disease manifestations. The scientific community continues to explore better vaccines for a range of serious and life-threatening disease conditions with the objective of eliminating their prevalence across the community environment. The timely administration of the approved vaccines to the intended recipients is highly required to challenge the progression and establishment of contagious, acute, and chronic disease conditions

References

1. 1.	Plotkin S. History of vaccination. Proc Natl Acad Sci U S A. 2014;111(34):12283–12287.
2. 2.	Smith KA. Edward Jenner and the Small Pox Vaccine. Front Immunol. 2011;2(21):1-6.
3. 3.	Hicks DJ, Fooks AR, Johnson N. Developments in rabies vaccines. Clin Exp Immunol. 2012;169(3):199-204.
4. 4.	WHO. Summary report on first, second and third generation smallpox vaccines. 2013. Available at: https://www.who.int/immunization/sage/meetings/2013/november/2_Smallpox_vaccine_review_updated_11_10_13.pdf.
5. 5.	Brown D, Fooks AR, Schweiger M. Using Intradermal Rabies Vaccine to Boost Immunity in People with Low Rabies Antibody Levels. Adv Prev Med. 2011.
6. 6.	Wnek K. Rabies. 2009. Available at: https://www.austincc.edu/microbio/2993q/rv.htm.
7. 7.	WHO. International travel and health. Tetanus. 2018. Available at: https://www.who.int/ith/vaccines/tetanus/en/.
8. 8.	Starlin Z. Tetanus. 2011. Available at: https://www.austincc.edu/microbio/2421b/tet.htm.
9. 9.	Blencowe H, Lawn J, Vandelaer J, Roper M, Cousens S. Tetanus toxoid immunization to reduce mortality from neonatal tetanus. Int J Epidemiol. 2010;39(1):i102–i109.
10. 10.	ARI. Polio vaccine developed. November 03, 2014. Available at: https://www.animalresearch.info/en/medical-advances/timeline/polio-vaccine-developed/.
11. 11.	WHO. Oral polio vaccine (OPV). Biologicals. 2018. Available at: https://www.who.int/biologicals/areas/vaccines/polio/opv/en/.
12. 12.	Sato Y, Sato H. Development of acellular pertussis vaccines. Biologicals. 1999;27(2):61-69.
13. 13.	WHO. Pertussis. Biologicals. 2018. Available at: https://www.who.int/biologicals/vaccines/pertussis/en/.
14. 14.	Ausielloa CM, Cassone A. Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace? mBio. 2014;5(3):e01339-14.
15. 15.	Tan LUL, Fahim REF, Jackson G, et al. A novel process for preparing an acellular pertussis vaccine composed of non-pyrogenic toxoids of pertussis toxin and filamentous hemagglutinin. Molecular Immunology. 1991;28(3):251-255.
16. 16.	Mak TW, Saunders ME, Jett BD. Primer to the Immune Response. USA: Elsevier; 2014.