Discussion Vaccination To Embrace or To Refute Biology

Discussion Vaccination To Embrace or To Refute Biology

Identify the strengths and weaknesses of both views.
Choose which view you agree with (only in the conclusion).
Explain why you agree with that view

Introduction
“The impact of vaccination on the health of the world’s peoples is hard to exaggerate. With the exception of safe water, no other modality has had such a major effect on mortality reduction and population growth” (Plotkin and Mortimer, 1988).

The development of safe and efficacious vaccination against diseases that cause substantial morbidity and mortality has been one of the foremost scientific advances of the 21st century. Vaccination, along with sanitation and clean drinking water, are public health interventions that are undeniably responsible for improved health outcomes globally. It is estimated that vaccines have prevented 6 million deaths from vaccine-preventable diseases annually (Ehreth, 2003). By 2055, the earth’s population is estimated to reach almost 10 billion (United Nations Department of Economic and Social Affairs, 2019), a feat that in part is due to effective vaccines that prevent disease and prolong life expectancy across all continents. That said, there is still much to be done to ensure the financing, provision, distribution, and administration of vaccines to all populations, in particular those which are difficult to reach, including those skeptical about their protective value and those living in civil disruption. Agencies including the World Health Organization (WHO), United Nations Children’s Fund (UNICEF), Gavi, the Vaccine Alliance, The Bill & Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Initiative (CEPI), with their multiple funding streams have been instrumental in expanding vaccine benefits to all. These importance of these organizations in global co-operation and participation was essential in the setting of the 2019 global pandemic of SARS-CoV-2, in light of the health and economic impact of COVID-19 on societies in high-, middle- and low-income countries.

Brief History of Vaccine Development
Human use of preparations to prevent specific infections have been described since 1500 AD, beginning in China (Needham, 2000) where smallpox was prevented by variolation, which is the introduction of material from scabs into the skin. In 1796 in the United Kingdom, Edward Jenner observed the immunity to smallpox of milkmaids having previously had natural infection with cowpox (Jenner, 1798). He determined that inoculating small amounts of pus from the lesions of cowpox, presumably containing a virus related to vaccinia, into susceptible hosts rendered them immune to smallpox. The vaccine against smallpox was developed in 1798. The next phase of scientific developments involving the manipulation of infectious agents to extract suitable vaccine antigens took almost a century of research. Louis Pasteur’s work with attenuation by oxygen or heat led to live-attenuated chicken cholera, inactivated anthrax and live-attenuated rabies vaccines at the turn of the 20th century (Pasteur, 1880, 1881, 1885). Alternative methods of attenuation using serial passage of Mycobacterium bovis led to the live Bacille Calmette-Guerin (BCG) (Calmette, 1927) vaccine, still in use today for the prevention of tuberculosis. Serial passage was also used in the development of yellow fever vaccines (Theiler and Smith, 1937a) which are grown in chicken embryo tissues (Theiler and Smith, 1937b). Whole cell killed bacterial vaccines were developed when methods to treat and kill bacteria through heat or chemicals were established and whole cell typhoid, cholera and pertussis vaccines resulted at the end of the 19th Century. In 1923, Alexander Glenny and Barbara Hopkins developed methods to inactivate bacterial toxins with formaldehyde, leading to the diphtheria and tetanus toxoid vaccines (Glenny and Hopkins, 1923).

Advances in virus culture in vitro allowed viral pathogens to be studied in greater detail and attenuation methods due to cultivation in artificial conditions led to the live oral polio, measles, rubella, mumps and varicella virus vaccines. In the 1960’s at the Walter Reed Army Institute of Research, vaccines were developed using capsular polysaccharides (Gold and Artenstein, 1971; Artenstein, 1975), of encapsulated organisms including meningococci and later pneumococci (Austrian, 1989) and Haemophilus influenzae type b (Hib) (Anderson et al., 1972). To protect against multiple serotype variants of polysaccharide capsules, polyvalent vaccines were developed and later conjugated to carrier proteins to enhance their efficacy in infants in particular by recruiting T-cell mediated help to induce memory B-cells (Schneerson et al., 1980). Vaccines made solely from proteins were rare, with the exception of the toxoid vaccines, but the acellular pertussis vaccine containing five protein antigens, was developed to mitigate the unwanted effects of the whole cell vaccine (Sato and Sato, 1999).

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The end of the 20th century marked a revolution in molecular biology and provided insights into microbiology and immunology allowing a greater understanding of pathogen epitopes and host responses to vaccination. Molecular genetics and genome sequencing has enabled the development of vaccines against RNA viruses possessing multiple variants of epitopes, such as the live and inactivated influenza vaccines (Maassab and DeBorde, 1985) and live rotavirus vaccines (Clark et al., 2006). DNA manipulation and excision allowed the use of surface antigen for hepatitis B viral vectors (Plotkin, 2014). The human papilloma virus (HPV) vaccine benefits from enhanced immunogenicity due to the formation of virus-like particles by the L1 antigen of each virus contained in the vaccine (Kirnbauer et al., 1992). Bacterial genome sequencing has provided in depth analysis of meningococcal antigens, to identify potential proteins for meningococcal B vaccines (Serruto et al., 2012).

Vaccine development was tested in 2020 when a novel coronavirus, SARS-CoV-2, emerged from China causing a severe acute respiratory illness, which subsequently spread globally. Within 5 months of the discovery of this virus (7th January 2020) (Zhu et al., 2020) and person-person transmission (Chan et al., 2020), 5,697,334 cases had been identified, with orders of magnitude likely not measured and almost no country escaped the pandemic. Owing to the previous advances in vaccinology, by 8th April 2020, there were 73 vaccine candidates under pre-clinical investigation (Thanh Le et al., 2020). Of these, six were in Phase 1 or 1/2 trials and one was in Phase 2/3 trials by 28th May 2020. The rapidity of this response demonstrated the ability to harness existing technologies including: RNA vaccine platforms (NCT04283461), DNA vaccine platforms (NCT04336410), recombinant vector vaccines (NCT04313127, NCT04324606) and adjuvants. The regulation, manufacturer and distribution of these vaccines will require expedition given the global public health need, from a period of many years to a matter of months. The efficacy and health impact of these vaccines is yet to be established, but if they are effective, then vaccines need to be made available for all global regions affected by SARS-CoV-2. The funding of this endeavor will prove challenging in a global context of national social and economic lockdown and massive government borrowing, but the justification for this provision will be through the multiple benefits to society that will need healthy citizens to rebuild economies in the decades post-COVID-19.

The history of vaccination is not complete without describing the public health intervention that led to the routine use of these vaccines for children globally. The Expanded Program of Immunization (EPI) was founded by WHO in 1974 with the aim of providing routine vaccines to all children by 1990 (World Health Assembly, 1974). In 1977, global policies for immunization against diphtheria, pertussis, tetanus, measles, polio, and tuberculosis were set out. The EPI includes hepatitis B, Hib, and pneumococcal vaccines in many areas and by 2017, 85% of the world’s children (12–23 months of age) received diphtheria, pertussis, tetanus, and measles vaccines (World Bank, 2019).

Health Benefits of Vaccination
Reduction in Infectious Diseases Morbidity and Mortality
The most significant impact of vaccines has been to prevent morbidity and mortality from serious infections that disproportionately affect children. Vaccines are estimated to prevent almost six million deaths/year and to save 386 million life years and 96 million disability-adjusted life years (DALYs) globally (Ehreth, 2003). The traditional measures of vaccine impact include: vaccine efficacy, the direct protection offered to a vaccinated group under optimal conditions e.g., trial settings; or vaccine effectiveness, the direct and indirect effect of vaccines on the population in a real-life setting (Wilder-Smith et al., 2017). Providing a numerical measure of vaccine impact therefore involves estimating the extent of morbidity and mortality prevented. In the United States in 2009, amongst an annual birth cohort vaccinated against 13 diseases it was estimated that nearly 20 million cases of disease and ∼42,000 deaths were prevented (Zhou et al., 2009). Infectious diseases that accounted for major mortality and morbidity in the early 20th century in the United States all showed over a 90% decline in incidence by 2017 from the pre-vaccine peak incidence (Roush and Murphy, 2007), due to high vaccine uptake of over 90% for the DTaP (diphtheria, tetanus, and acellular pertussis), MMR (measles, mumps, and rubella) and polio vaccines (World Health Organisation, 2019a; Table 1). A similar pattern of infectious diseases reduction was seen across other high-income countries, demonstrating the efficacy of vaccines when available and accessible.

Globally, the provision of vaccines is more challenging in many low- and middle- income countries (LMIC), as evidenced by the failure to make the EPI vaccines available to every child by 1990, irrespective of setting (Keja et al., 1988). Central to this is limited financial resources, but other barriers to vaccine introduction include: underappreciation of the value of vaccines locally/regionally though insufficient relevant data on disease burden, vaccine efficacy, or cost-effectiveness; inadequate healthcare infrastructure for vaccine handling, storage, programmatic management, and disease surveillance; and lack of global, regional or local policy-making and leadership (Munira and Fritzen, 2007; Hajjeh, 2011). In 2018, the global uptake of three doses of DTaP reached 86% which corresponded to 116,300,000 infants (World Health Organisation, 2019a). The vaccine coverage is, however, variable between low-, middle- and high-income countries because of a combination of economic and political circumstances as well as variable access to non-governmental support from Gavi, the Vaccine Alliance (Turner et al., 2018; Figure 2). Nevertheless, there has been a decrease in the global burden of diseases caused by vaccine-preventable pathogens (Figure 3) enabling healthier lives for many millions of children. A further benefit following vaccination, is the evidence that although vaccines may not always prevent an infection, for example VZV or pertussis, a milder disease course may follow (Andre et al., 2008; Bonanni et al., 2015).