Vaccines and Vaccine Resistance: Past, Present, and Future
Background
Edward Jenner is considered the father of vaccinology due to his use of cowpox virus to vaccinate against smallpox, which is a prime example of a live, attenuated vaccine.
In the first half of the 20th century, many vaccines became available for childhood diseases that had significant morbidity and mortality.
Global travel and trade led to an increase in the widespread transmission of diseases caused by microbes.
Objective
To offer a balanced view of the science behind vaccines, their current status, and expected advances.
To review the various public reactions to vaccines over the past decades.
Content
Provides a historical perspective of vaccine development.
Reviews mechanisms of vaccine-induced protection.
Discusses currently available vaccine technologies and vaccines.
Focuses on newer vaccines, including those utilizing viral vectors and gene-based vaccines.
Discusses messenger RNA vaccines in detail, given the time during which the narrative is written.
Conclusion
Vaccines have had a clear impact on human life.
Resistance and hesitation towards vaccines are not new and are not limited to the COVID-19 pandemic.
Continued development of vaccinology is necessary for further impact on human life.
A strong public health infrastructure is key to improving public awareness, proactive interventions, and appropriate vaccine utilization.
Preparedness for epidemics and pandemics should become more efficient.
Smallpox and Early Inoculation Attempts
Smallpox was one of history's most feared illnesses, with a death rate of 30% and serious morbidities.
Early attempts to intentionally infect (inoculate) people against smallpox were made in China and India.
The word “inoculation” comes from horticulture, referring to grafting a bud from one plant to another, and is now used interchangeably with “immunization”.
In China, scabs from healing smallpox pustules were ground up and blown into the nose of healthy people.
In India, a lance was used to inoculate material from a smallpox pustule into the skin of a healthy person through scratches.
In 1022 AD, a book mentioned using scabs from a recovering patient and grinding them up to give to healthy people.
Variolation, the practice of inoculation, was adopted in Europe in the 18th century, endorsed by Lady Mary Worley Montagu.
Variolation-induced smallpox caused 2–3% mortality and triggered outbreaks, leading to the practice becoming a felony in many parts of Europe.
The observation that dairy farmers did not catch smallpox led to safer inoculation methods.
Edward Jenner hypothesized that cowpox virus from cattle caused no or mild illness in dairy farmers, protecting them against smallpox.
In 1796, Jenner inoculated healthy people with pus from cowpox lesions and exposed them to smallpox, supporting his hypothesis that cowpox inoculation provided protection against smallpox.
Jenner's observations and experimentation are considered the birth of immunology, vaccine therapy, and disease prevention.
The term “vaccination” originates from the Latin word for cow (Vacca).
Impact of Vaccines Over Centuries
Vaccines have eradicated smallpox and are likely to eradicate poliomyelitis soon.
They have drastically reduced childhood mortality, increased life expectancy, and prevented lifelong disabilities.
Robert Koch established Koch's postulates in 1877, providing proof for the “Germ Theory” of disease.
Louis Pasteur (1885) prevented rabies in a young boy by injecting him with a weakened form of the rabies virus, calling it “Rabies Vaccine”.
The term vaccine has expanded to include live weakened or killed microbes, protein or carbohydrate components of microbial cells, and genetic codes for the antigen.
The first half of the 20th century saw an explosion of vaccines against whooping cough (1914), diphtheria (1926), tetanus (1938), influenza (1945), and mumps (1948).
Advances in technology boosted vaccine production in the late 1940s, making global vaccine campaigns and disease eradication feasible.
Global travel and trade escalated the potential for widespread transmission of diseases caused by microbes.
Vaccines against poliomyelitis (1955), measles (1963), rubella (1969), and others were added in the later part of the 20th century.
Smallpox, prevented by vaccination in 1796, was the first disease to be eradicated globally in 1980.
In the late 1990s, increasing world population and poverty led to a lack of or partial initial immunization of children in developing countries.
In 2000, the Bill and Melinda Gates Foundation and partners set up the Global Alliance for Vaccines and Immunization (GAVI).
GAVI encouraged vaccine manufacturers to lower vaccine prices for less resourceful countries in return for high volume and long-term predictable demand, preventing thirteen million child deaths.
Infections caused by new and emerging pathogens appeared as many from the past were being controlled by vaccination.
In response to the 2014/2015 Ebola Virus epidemic, the world prepared to handle such epidemics better.
The Coalition for Epidemic Preparedness Innovation (CEPI) was launched in 2017 to accelerate the development of vaccines against emerging infectious diseases and enable equitable access for affected populations during outbreaks.
The first vaccine against Ebola was approved by the US FDA and EU regulators in 2019, and a second received approval in Europe in 2020.
The time between the start of the first phase 1 trial (October 2014) to the approval of the first vaccine (Nov 2019) was five years, compared to a typical 10-15-year timeline for vaccine development.
Mechanisms of Vaccine-Induced Protection Against Infections
Vaccine immunology and generation of vaccine-induced protection depend on interaction between multiple compartments of the host immune system.
Early protective efficacy is measured by the detection of antigen-specific antibody.
Higher levels of antibodies generally correlate with better protection.
The quality of antibodies, including specificity, affinity, avidity, bactericidal activity, and neutralizing activity, are major determinants of efficacy.
For long-term protection, the antibody response needs to persist above a threshold level.
In the absence of such a level, the vaccine needs to induce and maintain immune memory cells that can rapidly and effectively reactivate with subsequent exposure to the same or related microbe.
Effector mechanisms of vaccine-induced immunity include both cells and the products they secrete.
Antibodies secreted by B lymphocytes bind to specific antigens on the microbe or to their toxins.
CD4 or T-helper cells (Th1 and Th2) produce cytokines and support the generation and maintenance of B lymphocytes.
T helper cells defend against extracellular bacteria by recruiting neutrophils and inducing local inflammation.
Follicular T-helper (Tfh) lymphocytes support the activation and differentiation of B lymphocytes into antibody-secreting cells.
Cytotoxic or CD8 lymphocytes contribute to the immune response by recognizing and killing infected cells and by secreting antiviral cytokines.
Regulatory T (Tregs) lymphocytes control the effectors by maintaining immune tolerance.
Most microbes, their antigens, and the vaccines for them trigger both B cell and T cell responses.
CD4 T cells are required for antibody responses by B cells (humoral immunity) against extracellular pathogens.
Antibodies significantly influence T cell (cellular Immunity) responses to intracellular pathogens.
The nature of the antigen or vaccine directly influences the recruitment of various types of effectors and resulting protective efficacy.
Capsular polysaccharides of bacteria like Streptococcus pneumoniae and Neisseria meningitides elicit B cell responses in a classically T-independent response.
Once conjugated to a protein carrier, the peptide antigen recruits antigen-specific CD4 T cells, transforming the response to T-dependent.
T-dependent responses are also elicited by protein antigens, toxoids, inactivated and live attenuated viral vaccines.
T-dependent immune responses offer high affinity antibodies and immunologic memory.
Memory B cells are generated only during T-dependent immune responses through germinal center and follicular T helper cells.
Memory B cells are resting cells and do not produce antibodies; upon re-exposure to antigen, they rapidly differentiate into antibody-secreting plasma cells that produce higher affinity antibodies than the primary plasma cells.
The induction of strong CD8 (Cytotoxic) T cell responses require live vaccines, vectors, or novel delivery systems.
Currently Available Vaccine Technologies
Live-attenuated Vaccines (e.g., mumps, measles, rubella).
Killed Inactivated Vaccines (e.g., poliomyelitis, hepatitis A).
Toxoid Vaccines (e.g., diphtheria, tetanus, acellular pertussis).
Conjugated Vaccines (e.g., pneumococcal, meningococcal).
Subunit vaccines (e.g. influenza, typhoid).
Recombinant Vaccines (e.g., hepatitis B, human papilloma virus).
Viral vector vaccines (e.g. ebola, dengue).
Chimeric Vaccines (e.g., dengue).
Routine Infant and childhood Vaccines recommended by CDC are listed at … [5].
Routine Adult Vaccines recommended by CDC by age group and underlying medical conditions and travel to endemic areas are listed at … … [5].
The first five categories of vaccines are made by conventional technology.
All use a) a microbe (live attenuated or inactivated; b) a part of it e.g. capsular polysaccharide of Pneumococcus, Meningococcus, Hemophilus type B conjugated to proteins to optimize their immunogenicity; c)Toxoids modified from toxins produced by the bacteria that are involved in pathogenicity; d) Subunits of the microbial cell.
Despite advances in technology, mass production of these vaccines remains expensive and time-intensive.
Virus-like particles made by recombinant and viral vector technology have greatly facilitated and streamlined vaccine production.
Viral Vector Vaccines
Viral vector vaccines are a cross between live attenuated and gene-based vaccines.
The virus carries the gene encoding the antigen of interest (e.g., the EBOV glycoprotein of Zaire ebolavirus that replaces the gene of the carrier Vesicular Stomatitis virus).
The vector virus carrying the code enters the cell, which then transcribes and translates the gene to produce the antigen.
An immune response is generated by the antigen displayed on the cell surface.
The process may be amplified by slow reproduction of the vector virus with the infection of more cells and production of more antigen.
Preexisting immunity against any part of vaccine can limit its effectiveness.
Depending on the vector used, geographic variation in preexisting immunity poses a major challenge.
DNA and RNA Vaccines do not pose this challenge.
If the vector in a vaccine is cleared before it gets into cells, the immunogenic moiety never reaches its target.
The low neutralizing antibody elicited in a phase 1 trial of a candidate CoVID 19 Vaccine with human Adenovirus 5 as the vector was attributed to this phenomenon.
The CoVID 19 Vector vaccine developed in England uses an adenovirus that infects chimpanzees (Ch Ad OX1/A2 D1222) but not humans; however, the possibility of cross-reacting preexisting immunity is a possibility.
The one with emergency use authorization in the US contains a sero-group D recombinant Adenovirus 26. Despite significant seroprevalence in certain adult populations, neutralizing antibodies against Ad26 remain much lower than against Ad5.
The Vaccine developed in Russia consists of the gene for whole S protein of CoVID 19 contained in two different recombinant human adenoviruses.
Gene-Only Based Vaccines
The immunization method using genetic material to encode for the desired antigen depends on the production of immunizing protein by the cells into which a small part of the genetic code has been introduced.
Finding the genetic code has become relatively easy and fast using currently available technologies.
Gene-only based vaccines are faster and cheaper to produce in large quantities compared to conventional vaccines.
DNA Vaccines
Part of the pathogen's DNA known to code for protein/proteins responsible for eliciting a protective immune response is injected.
The genetic material must enter the nucleus of the host cell, which can happen only when the cell is dividing, creating an inherent inefficiency in the process.
Once in the nucleus, the DNA creates mRNA, which travels back into the cytoplasm; this mRNA leads to protein/antigen synthesis.
Peptides derived from the protein are presented on the cell surface and stimulate the lymphocytes responsible for generating an immune response.
The breadth and depth of the immune response evoked by DNA vaccines are not fully clear yet; they usually encode one protein from the pathogen.
If a protective immune response involves multiple proteins, multiple vaccines will need to be mixed together.
Plasmids can act as a transport for the DNA vaccines.
Alternatively, electroporation (electric pulses) can be used to create temporary openings in the cell membrane to let the vaccine get into the nucleus.
The potential value of DNA vaccines lies in their capability to get the end result of protective immunity without the need for handling a virulent pathogen or adapting the pathogen (or its parts) to manufacturing processes.
A biopsy from cancerous tissue can be used to make personalized antitumor DNA vaccines.
DNA vaccines move T-helper responses to Th1 phenotype, so they are under development for allergic and autoimmune disorders.
Four animal health products for large animals (horses and pigs) are licensed currently: two are prophylactic vaccines against infectious diseases, one is a hormone gene for food animals, and the fourth is for cancer chemotherapy.
The successful use of DNA molecules in large animals, compared to the relatively disappointing efficacy of DNA vaccines in human clinical trials, is being further investigated. Advances in delivery and expression technologies to increase the potency of DNA vaccines in humans are underway.
Regulators have granted emergency approval for the world's first DNA vaccine for human use, one of the many vaccines being used to fight the currently ongoing CoVID 19 pandemic.
Messenger RNA (mRNA) Vaccines
Messenger RNA (mRNA) AND first proteins produced by isolated mRNA in the laboratory were discovered in 1960s [9–15].
RNA in general is considered extremely unstable.
mRNA was synthesized in the laboratory in mid 1980s but seen to be too unstable for use directly as a drug or vaccine.
Its development into a drug or vaccine was therefore deemed to be too expensive. to be used in therapeutics, a stabilization method would be essential.
In 1965, lipid molecules were synthesized into lipid envelopes called Liposomes with the potential of delivering otherwise difficult to deliver molecules to cells for treatment and/or prevention of diseases. liposomes are made of positively charged lipids.
A major mile stone happened between 1987 and 1989 when synthetic mRNA was introduced into cationic liposomes and delivered to human cells and frog embryos. this led to liposome wrapped mRNA being delivered to mice and then tested as treatment in rats.
The first mRNA vaccine was tested in mice against influenza in mid 1990s.
For the next ten years the lack of resources and resistance to commercialization hindered the development of mRNA as a therapeutic/preventive agent.
However, a large number of scientists in various institutions continued to work at its potential independently and in collaboration.
The potential use of mRNA (vaccine) as a therapeutic agent to treat cancer was received favorably by cancer immunologists.
It was proposed in 1997 that introducing synthetic mRNA into immune cells from blood of the patient would allow the cells to produce tumor proteins encoded in mRNA. once injected back, these would instruct the immune system to attack the tumor cells.
A late stage cancer candidate vaccine failed in a large trial. However, the concept inspired the founders of two German companies (two of the largest mRNA companies in existence now) to do the same with administration of mRNA directly into the body.
The ability of directly injected mRNA to elicit an immune response had been reported earlier in mice [12]. however, their use as a vaccine against human immunodeficiency virus had been shown to set off massive inflammatory reactions when injected into mice.
In 2005, the same researchers reported that rearranging the chemical bonds on one of mRNA nucleotides, uridine, creates an analogue called pseudo uridine. this substitution allowed the mRNA to escape innate immune system.
Many experts believe that pseudo uridine is an essential component of mRNA vaccine technology. both mRNA vaccines in use currently against COVID 19 contain modified mRNA.
Other approaches under investigation are a genetic modification to mRNA minimizing the amount of uridine in candidate vaccine and use of unmodified mRNA.
In parallel, a scalable method for manufacturing Lipid Nano particles (LNPs) was described in 2005. the first clinical trial of a mRNA vaccine in LNPs was done against influenza in 2015.
The nano-particles have a mixture of four fatty molecules. the first called an ionizable lipid converts the positively charged LNPs under laboratory conditions to a neutral charge under physiologic conditions limiting their toxicity. the ionizable lipid is the key to LNPs function while the other three contribute to structure and stability.
A new method of mixing and manufacturing LNPs involves using a T- connector apparatus to combine fats (dissolved in alcohol) with nucleic acids (dissolved in acidic buffer). when the two solutions merge, the components spontaneously form densely packed LNPs. this has proven to be a more reliable technique for making mRNA-based injectables.
All marketed and candidate CoVID vaccines contain closely related LNP concoctions.
By the beginning of 2020, moderna was working on nine mRNA vaccine candidates for infectious diseases without a huge success. within days of CoVID 19 genome sequence becoming available, moderna created a prototypic vaccine. collaborative work with US national institute of allergy and infectious diseases led to mouse studies and launch of clinical trials within a short period of ten weeks. biontech in germany partnered with pfizer in new york to conduct clinical trials.
It took less than eight months from first human testing to emergency authorization of two CoVID 19 mRNA vaccines. the triangle of this unprecedented success is cornered by a) availability of CoVID 19 genetic sequence, b) modified mRNA technology and c) lipid nano particle technology.
With unprecedented impact on human race. both vaccines contain sequences that encode CoVID 19 spike protein as the immunogen to induce protective immunity. other approaches to antigen use are being studied [16]. the mutated spike protein (G 614) of delta variant renders CoVID 19 more infectious. this structural characteristic of the spike protein G 614 makes a formidable antigen also for future vaccines.
The mRNA technology lends itself to use of codes for multiple corona viruses since mRNA gets into the cytoplasm with 95% of cells taking it up to make protein much more efficiently than DNA. mRNA cannot cause infection. it does not enter the nucleus and chances of integration into DNA are low. it cannot cause infection. the body breaks down mRNA and its LNPs within a few hours alleviating concerns about long term risks.
An informal comparative evaluation of mRNA, viral vector and inactivated vaccines against CoVID 19 show mRNA vaccines to have the highest efficacy (95%) compared to 75% and 50% for the other two types. as expected with any pharmacologic intervention, we have seen minor side effects and few major adverse events with all types of CoVID vaccines. there is also a question of antibody dependent enhanced (ADE) break through infections with any of the CoVID vaccines [17] this phenomenon seen with dengue viruses is less likely because corona virus severe disease is not centered around infants, children or individuals with previous corona virus infections.
Vaccination of laboratory animals by SARS or MERS viruses followed by live virus challenge resulted in vaccine hypersensitivity (VAH) reactions similar to those seen in humans with inactivated measles or respiratory syncytial virus vaccines. this phenomenon will need to be entertained and avoided in future vaccination against corona viruses.
Vaccine Skepticism and Resistance
A quick visit to the past is necessary to put current events in perspective.
Variolation, a practice to intervene in smallpox transmission, served as a precursor to the discovery of vaccination against smallpox.
Chinese Buddhist nuns documented the use of dried and ground scabs (from patients recovering from smallpox), given by nasal insufflation to healthy people.
After variolation, cases were treated as if they were infected, the same as those who had acquired the disease naturally. Today, this would be considered immunization with a live attenuated virus followed by precautions to limit its transmission to others.
The procedure was carefully performed by “experienced elderly women” resembling the concept of “birthing ladies”.
The inoculation method used in India spread to other parts of Asia, Africa, the Middle East, Europe, and the Americas.
Physicians in Europe used the practice often with positive effects on the demographics of small population groups.
John Williamson's methodical and safe approach in the 18th century was well described by Brian Smith in 1998.
At the time, the minor form of smallpox caused death in 1%, and the major form caused death in about 30% of those infected. Some epidemics in highly susceptible, previously unexposed populations resulted in death rates as high as 50% [19]. In experienced hands, the death rate in variolated patients who developed smallpox was 0.5–2%. This was enough to have detractors, oppositions, and serious debates.
Historically, this would be the beginning of what is currently called “AntiVaxxers”.
In 1706, North American Reverend Cotton Mather learned about inoculation being used against smallpox.
He discussed the practice with local physicians, who learned variolation and used it in their family and servants when smallpox arrived in 1721. At the end of the epidemic, 14% of people with natural smallpox died compared to 2% of those variolated.
In 1768, Catherine the Great of Russia variolated herself and her family, followed by two million citizens.
Around the same time, in Norfolk, Virginia, Archibald Campbell convinced a group of people to receive variolation. On June 27, while he and Dr. John Dalgleish were inoculating people at his home, a mob attacked his home.
The tension between for and against groups came to a head ending in the ban of the practice in 1770 by the Virginia Legislature.
General Washington in 1776 was suffering from losses of troops to smallpox brought by British soldiers. He ordered inoculation (sometimes by force) of new recruits while they were in training, which gave them the time to recover from the symptoms from inoculation or a mild form of the disease.
Between 1796 and 1798, Edward Jenner used material from cowpox lesions to vaccinate people. He published evidence of protection against smallpox by vaccination that was safer than variolation. Also, the vaccine could self-maintain itself by arm to arm transfer.
There were detractors and resisters, but science and prudence won. This was followed by the decline of variolation, which was made illegal in many countries, the first being Russia in 1805.
It was only during WHO's global smallpox eradication campaign (1966–1980) that the last remaining and hidden Variolation programs were ended in Afghanistan and Pakistan.
In 1891, Louis Pasteur, in honor of Edward Jenner, widened the term Vaccine/vaccination to refer to the artificial induction of immunity against infectious diseases in general.
Louis Pasteur's extension of the principle of vaccination, his work, and that of his successors has led to the development of many effective vaccines against infectious diseases, including diphtheria, measles, mumps, and influenza.
The second disease (after smallpox) targeted for global eradication by vaccination is Poliomyelitis.
But for vaccination, the world would be in the medical dark ages.
The concept of Variolation in essence has survived through the centuries in the form of practices like “Pox Parties” in which well children were intentionally exposed to diseases like measles, rubella, and chickenpox. This practice persists despite strong disfavor from public health authorities [20].
The facial masking to reduce the impact of CoVID 19 has benefits similar to that of variolation [21]. The hypothesis was that “Universal masking would become a form of variolation that would generate immunity and thereby slow the spread in the United States and elsewhere while we await a vaccine”.
Vaccines, not just a vaccine, arrived at an unprecedented speed, but so did the Vaccine skepticism and resistance from expected and unexpected sources. This has made an easily accomplishable goal of “mass Vaccination” in countries like the United States difficult to accomplish.
As long as there are unvaccinated populations even smaller than those vaccinated, the reservoir persists for ongoing transmission. So nothing under the sun is new, including the very basic human characteristic of controversy about a vaccine against the virus that looks like the sun.
With the mandating of smallpox vaccination in Europe in the early nineteenth century for certain groups, societies of Antivaccinationists formed to protest unequal treatment and infringement of individual liberty [22]. Later that century, antivaccinism spread to the United States and persists in the form of AntiVaxxers.
The modern era of vaccination got underway in the late 1950s with the arrival of vaccines to prevent poliomyelitis, measles. mumps and rubella. the poliomyelitis vaccine released in 1954 was greeted with enthusiasm. people knew poliomyelitis as a dreaded disease and were desperate to prevent it. a few voices did speak against the vaccine but coercive policies never became necessary.
The vaccines of the 1960s for measles, mumps, and rubella were not received with the same enthusiasm. Mumps was seen as a mild disease in general, with only some adult men suffering the most serious sequelae. Some in the medical community proposed giving this vaccine only to post-pubertal boys who had not yet suffered from the disease.
Deeper studies of the disease at the CDC rendered it more serious with more reasons to vaccinate all children against mumps. The federal advisory committee for immunization practices (created in 1964) recommended in 1977 that all children get the mumps vaccine along with other childhood vaccines at the time. It is easy to understand why such events would cause confusion in the lay public's mind, leading them to question vaccines in general.
The blossoming of the social movement with the focus on questioning authority and experts coincided with the stricter approach to the vaccine schedule and its enforcement. Similar to the push back against patriarchy by women, against industry by environmentalists, there was push back against doctors and public health authorities recommending vaccines.
Patients, right and women's health movements led to the discovery of “unexpected” problems with vaccines by mothers who shared them in resources like Mothering magazine. The additive to vaccines like aluminum, mercury, and formaldehyde became topics for scientific and public debate.
An hour-long news report “DTP: Vaccine Roulette” aired in 1982 and ended with conflicting statements about the use of DPT in children with a history of seizures from a vaccine scientist and the American Academy of Pediatrics.
“Dissatisfied Parents Together,” an organization of parents inspired by then-current events, advocated for safer vaccines, greater government oversight, and federal compensation for the families of children harmed by vaccines. The founders of the organization co-authored a book “DPT: A Shot in the Dark” (1985), detailing the struggles of parents of children who had been harmed by vaccines.
The harmful effects of DPT were compared to those of environmental chemicals like pesticides. The National Childhood Vaccine Injury Act (1986) was the result of the efforts of this organization.
The vaccine schedule for children has continued to expand, as has the dialogue and debate about the vaccines. The debates echo those from the nineteenth and early twentieth centuries in the form of a) Is it necessary? b) Is it safe? c) Can the expert advice about it be trusted?
The vaccine skepticism of today is rooted in the social movements of the post-World War II era. These movements prompted a generation of adults to question drugs, doctors, environmental contaminants, and authority in general.
Over time, the armamentarium of drugs and the mandatory vaccine schedule for children increased, while less and less previously fatal childhood infectious diseases were being seen. Of course, the later was the effect of the vaccines. It was like what was not being seen, did not happen.
Smallpox was eliminated in 1980, and the eradication of poliomyelitis globally seems to be in sight. On the other hand, the US declared measles eradicated in 2000. However, after a 22-year-long Measles Vaccine campaign, the disease is back [23].
The role of vaccine-skeptical celebrities, including Jenny McCarthy and now-discredited Dr. Andrew Wakefield, were the products, not necessarily the cause, of today's parental mistrust of public health authority and vaccines.
The Lancet 1998 publication led by Wakefield on measles vaccination and autism added fuel to the fire. Jenny McCarthy, mother of a child with autism, wrote and spoke about how she saw vaccines trigger her son's autism.
Reassurances about new vaccines came along with new rationales for vaccination, e.g., vaccinating children to protect adults and to protect economically productive time for parents. Although rational, these advances in immunology and molecular biology provided room for further controversy.
The struggle between vaccine laws, mandates, and vaccine skepticism was born during the dawn of variolation and shows no signs of a final resolution.
The debate has periodically quieted in the face of war, new cultural and economic preoccupations, and new epidemics. The current, not so new pandemic of CoVID 19 would have been expected to be one such time in human history. The arrival and uptake of multiple vaccines with scientifically proven risk-benefit ratios at warp speed would have been greeted and celebrated. Instead, we are facing unprecedented resistance from population groups of different cultures, religions, races, educational backgrounds, economic resources, and demographics [24].
Events like the Tuskegee Syphilis Study have been cited as medical atrocities and explain the distrust of the US black community in the healthcare system [25]. Obviously, not enough has been done to shed the fears of those horrendous acts of medical brutality against society.
Medical science has progressed at a much faster speed in the 20th and early 21st centuries than anticipated, as has communication science. Every bit of new development is used as “news” by multiple media uncountable times a day, followed by explanations and commentaries by multiple “experts” in “bite-size” formats.
Often, different experts use different verbiage, their own interpretation of data, and sometimes downright misinformation. The multitude of “interpreters” and sources on the one hand and the public's little knowledge (not better than ignorance) on the other hand have created a mountain out of a molehill.
What is lacking at the grass roots is public health education provided during good and bad times as honest, scientifically proven information in an easily assimilable language and format. The information needs to be disseminated to the public by people on the ground who are actually providing medical care to the communities. Their recommendations are what people follow in their daily lives.
The medical information collected by state public health authorities and fed to the CDC on epidemiology should go to the public through this resource. The National Institutes of Health, FDA, and CDC should be responsible for providing the information on drugs and vaccines to the medical providers. It is obviously good to have this information open and accessible to the public as an added resource.
What can be done in a hurry? Previous work has used two major approaches to increase vaccination rates [25,26]. The first approach focuses on those who are uncertain about vaccination and aims at boosting vaccine uptake intention. Recognizing that changing intention does not always translate into action, the second approach involves helping with the follow-through of vaccination intentions and overcoming variables like forgetfulness, hassle costs, and procrastination.
Dai et al. published a study on the role of behavioral nudges in increasing CoVID 19 vaccine uptake [27–29]. They conducted two randomized clinical trials at the University of California, Los Angeles. Nudges, defined as interventions to alter the behavior of people in a predictable way without forbidding any options or changing economic incentives, were used to improve the uptake of the COVID vaccine.
The starting point for the trials was Jan 20, 2021, and participants were drawn from the UCLA Health primary and specialty care attributed patient list. As they became eligible for the vaccine, UCLA Health enrolled them in two sequential large-scale randomized controlled trials to study the impact of nudging followed by carefully designed reminders to reduce barriers to the vaccine uptake.
The reminders were combined with additional interventions, including a) behaviorally informed messaging designed to amplify the desire of individuals to get vaccinated, b) a traditional information provision intervention aimed at correcting the misconceptions involved in vaccine hesitancy.
The findings of these research studies highlight that behavioral science insights and carefully designed interventions at close to zero marginal cost can increase and speed up CoVID vaccination. Combining reminders with a video-based information intervention did not increase vaccination further.
Of the participants who made an appointment for the first dose, only 10% did not show up, and 90% of those who received the first dose scheduled their second dose. Thus, getting started, i.e.; coming for the first vaccination, is the biggest barrier. This has previously shown to be the case with Hepatitis B vaccination of infants.
Natural fear of the unknown and organized conspiracy by government will remain. But many other things are amenable to change. It is important to recognize that modern-day parents have not suffered and, for the most part, seen in others the diseases prevented by childhood vaccines.
Raising the awareness of those diseases is of utmost importance. Adult immunizations are often not a part of routine care in most parts of the world and are suboptimal in the USA. During the pandemic, people of diverse educational backgrounds are expected to comply with something new and unusual. Lack of public awareness that shots are not just for babies is a serious concern and can be rectified with simple and inexpensive ways.
The last but definitely not the least important is to uncover for the public the myths about antimicrobial agents i.e, their lack of for most viral diseases and their shortfalls and pitfalls for bacterial diseases. the inherently changing nature of microbes particularly under the threat of indiscriminate antibiotic use with ensuing resistance to the few still active is a more needed public health message than the often misunderstood “hype” heard everywhere these days.
Incurable and/or untreatable chronic illnesses are an accepted fact. what needs to become a fact that many acute illnesses in the field of infectious diseases are not only untreatable but also transmitted to families, friends and the rest. what would be a better time than now for this lesson.