Vaccines: History and Future

By Kirthi Tennakone-May 18, 2020, 10:12 pm

We live in an environment of billions of microorganisms existing almost everywhere. A large proportion of these are symbiotic or harmless but few pathogenic varieties invade bodies of humans and animals causing disease. As a result of exposure to these organisms for ages, the advanced forms of life evolved strategies to prevent their invasion and eliminate the intruders. Pathogens evade defense framework of the host and exploit its resources. To counteract this danger, the host develops specialized weapons termed antibodies. They are tiny entities released to the blood or cellular fluids capable of identifying the enemy and destroy. Each type of bacteria or virus can be dealt with only by a specific antibody and the system takes some time to design it.

It is uneconomical to maintain a variety of antibodies produced in encounters with different pathogens. Therefore only the items equivalent to samples are permanently retained. If a future invasions occur these samples facilitate rapid manufacture of relevant antibodies, saving the time taken for designing.

The above mechanism referred to as immunological memory is the basis of vaccination. Here a less virulent or tamed version of the pathogen or an agent that mimic it is introduced to healthy people, when the mild reaction create antibodies retaining the know how to make them again, if the need arises.

Today, more than ever before, the whole world diverts attention to the question of vaccines for combating COVID-19. The idea of vaccines, one of greatest achievements of modern science, first originated as a means of preventing smallpox.

SMALLPOX AND VARIOLATION

Smallpox a dreadful contagious disease caused by the virus Variola major had existed for more than 6000 years. Although its origin remains uncertain, the virus probably jumped from rodents to humans in East Africa. As the world population increased segregating people to cities, outbreaks occurred frequently when traders dispersed the infection worldwide. During the 18th century, smallpox was the major cause of death, 30 -50% of the infected people died and those survived acquired lifetime immunity. Healed pustules disfigured the face of survivors. Men and women with such symptoms were frequently seen in streets those days.

Around early 1600s Chinese Buddhist monk physicians deliberately infected people with smallpox virus to render them immune. In this technique referred to as variolation, fluid taken from a pustule of a smallpox patient is introduced into an incision in the skin. Most inoculated persons developed a mild form of the disease and healed without disfiguration. Few contracted the full blown disease and survived with scars or died. Subsequently, use of a less virulent strain of the smallpox virus reduced mortality after variolation. The idea of variolation reached Middle East via the Silk Road and widely practiced in Turkey. Europe learnt the technique from Turkey, but was hesitant to adopt because of the risk and religious concerns. Some argued that smallpox is a punishment from heavens, humans were not supposed to intervene. Nonetheless, several prominent persons advocated variolation to reduce the agony of smallpox. Lady Mary Montagu, wife of a British Ambassador to Turkey, learnt the art of variolation in Turkey. Disguised as a man she gained access to a mosque and observed the inoculation procedure. Later she variolated her daughter and persuaded authorities in England to adopt the practice. James Jurin, mathematically inclined physician and the Secretary to Royal Society, conducted a statistical analysis, concluding benefits of variolation outweigh the risks. Mathematical genius Daniel Bernoulli, performed a calculation and told the French Academy of Sciences, if children are inoculated before the age 5 years, then young men and women 26 years old in the world will be increased by 15%. When Britain gradually accepted variolation, Voltaire – the key literary figure of European enlightenment, wrote a strongly worded essay, denouncing France for banning this method of limiting the spread of smallpox. Declaring contents of the essay and his subsequent satirical attacks on King’s Attorney General as averse to viewpoint of the theologians, Voltaire was arrested for blasphemy. Writing from the prison Voltaire persuaded the Empress of Russia, Catherine the Great, who had a good rapport with the intelligentsia of Europe to follow Britain and introduce variolation. The Empress got herself, her son and the members of the Royal Court inoculated, to set to an example. Voltaire praised the Empress for legalization of smallpox inoculation, again levelling criticism against French authorities. France was the last European country to legalize variolation.

Variolation was introduced to America, when a severe epidemic ravaged Massachusetts in 1721. The newspaper ‘New England Courant’ under editorship of 16 year old Benjamin Franklin - who later turned out be a scientifically literate statesman, frequently criticized the practice of variolation. His 4 year old son died of smallpox in 1736. Later giving advice to citizens, Franklin said ‘no parent should be forgiven if a child not inoculated dies of smallpox’.

SMALLPOX AND VACCINATION

In 1757 smallpox epidemic broke out in England and large groups of children were variolated by a reputed physician. Among the children treated, there was an 8 year old orphaned boy named Edward Jenner. This talented boy completed primary education and qualified as a doctor after 7 years of training in a medical school, returned to the village and practiced as a country doctor. One day when the whole village was scared by the news of a smallpox breakout in the vicinity. Edward Jenner heard a pretty talkative milkmaid uttering "I will never get my face pockmarked, I had cowpox". Inquisitive Jenner noted none of the other milkmaids in the village showed signs of smallpox contraction. Cowpox doesn’t turn deadly to humans, it developed few pustules on the hand where the virus enters during milking.

To test the hypothesis, Jenner took a smear from a cowpox lesion in the right palm of the milkmaid named Sarah Nelms and inoculated it to his gardener’s 8 year old son James Phipps. Three weeks later he was subjected to a similar treatment using material extracted from a pustule of a smallpox patient. Even after repeated smallpox pathogen inoculations, Phipps never contracted disease. Jenner described his procedure as "vaccination", because the source of the original inoculum had been a cow "vacca" in Latin. Despite opposition of the religious orthodoxy, vaccination gained ground as a remarkable development in preventive medicine.

SMALLPOX AND VACCINATION IN SRI LANKA

Ancient Sri Lankan history refers to instances of epidemics, some of these may have been smallpox outbreaks. The first record of a smallpox epidemic is probably the one that stuck Trincomalee around 1578, when Dona Catherina was orphaned by death of her parents after contracting smallpox.

A severe outbreak of smallpox occurred in Kandy 1697 during the reign of the King Wimaladhramasuriya. King his officials and elites left the city fearing of contagion, leaving poor in the city. The sick were confined alone to their dwellings or moved to huts in the thicket, often murdered and eaten by leopards and jackals.

When the missionary Father Joseph Vaz and his nephew came to Kandy, premises were strewn with the dead and the dying. In an unprecedented compassionate effort they nursed the sick providing food and arrangements for shelter. Similar sporadic epidemics had occurred in Sri Lanka until vaccination was introduced.

In 1802 Ceylon Colonial Government initiated public vaccination. There were public hesitancies to vaccination, pointing various reasons: a curse of a female deity bring forth the disease, offerings to her is the remedy but not vaccinations; getting vaccinated was tantamount to stamping allegiance to British; the smell of smallpox sores attract leopards and the wound at the site of inoculation could lead to the same consequence. Nevertheless, by and large, the response to vaccination in Sri Lanka was favourable compared to other regions in Asia. When vaccination campaigns were held Mudliyas, Village Headmens and other community leaders came forward to get vaccinated. In the 1816 vaccination program in Kandy, Kappetipola Disawe and his sons got vaccinated.

After introduction of vaccination, incidence of smallpox in Sri Lanka declined. Few years before World War II cases of smallpox rarely surfaced. However a major outbreak occurred during wartime, when containment measures were derailed. Last one was in 1961 with 44 cases.

ERRDICATION OF SMALLPOX

One would think that in order to fizzle an out a disease like smallpox forever each and every individual in the globe needs to be immunized – which is a practical impossibility. Newborns and convalescents cannot be vaccinated immediately. Some avoid and every nook and comer cannot be reached to vaccinate people.

In 1760, Swiss mathematician Daniel Bernoulli, analyzed effectiveness of immunization in reducing the incidence of smallpox. Subsequent extension such calculations revealed that to eliminate smallpox completely, vaccination of around 70% of the world population is sufficient - a criterion technically known as achieving heard immunity threshold. Based on this idea, WHO organized a program in 1958 to rid the world of the malady. The plan which didn’t move fast owing shortage vaccine and other resources was invigorated in 1967, eliminating pockets of disease in Asia, Africa and Latin America.

Bangladesh girl Rahima Banu 3 years old in 1975 was the last person to contract smallpox naturally and acquire immunity. On 8th May 1980, World Health Assembly declared world has been freed of smallpox.

OTHER VACCINES

Today vaccines are available for immunizations against viral diseases; polio, measles, mumps and bacterial diseases; whooping cough, diphtheria, typhoid etc. Vaccines offer two benefits. When you give polio vaccination to your child, he or she will not get polio. If around 80 % of the population in the country are immunized by vaccination, the region could be made free of polio. Polio is now endemic only few parts of the world. Intensified efforts of vaccination would to rid world of polio in near future. Measles is to harder to eradicate because heard immunity threshold here is over 90%. A few refusing measles vaccination for their children and unavailability facilities in deprived regions, constrain the achievement of the required level of immunization.

A VACCINE FOR COVID

As a topmost priority, whole world inquisitively awaits a vaccine to prevent COVID. Pandemics in olden days came to a halt, possibly because of natural immunization reached the heard immunity threshold, sacrificing a significant percentage of the population - today we cannot allow this happen. Social distancing, isolation and other control strategies effectively lower this threshold, however these measures cannot be continued indefinitely. Therefore a vaccine would be the only conceivable solution.

After discovery of the first vaccine – the one for smallpox, other promising methods of making vaccines emerged. There are two types of older generation vaccines - live attenuated and inactivated. In the former, inoculation of a weakened live agent related to the pathogen induces immunity, whereas in the latter, killed disease causative microorganism itself or one its relatives, trigger antibody production. Live vaccines though more potent poses the risk of infecting those with compromised immunity. Newer vaccines adopt more advanced techniques to enhance potency and ease large scale production. One strategy recently researched has been to encode immunity driving traits of the coronavirus to a relatively harmless virus and design a live vaccine based on this genetically engineered organism. Other alternative is finding ways to introduce viral genetic material into the cells and allow multiplication inducing immunity. Over one hundred groups worldwide strive hard to develop COVID vaccines. Although quite promising results have been obtained, it is difficult to give definitive answer to question when the vaccines will be available.

The other issue is production of sufficient quantities of vaccine at an affordable cost and distribute the product equitably. The calculated value of the heard immunity threshold for COVID is approximately 60%, meaning this percentage of people in the world needs to be immunized to eradicate the sickness. Immunization of 60% of the world’s population in a short period require an unprecedented upscaling of vaccine manufacturing technology.

Unknowns in the nature of COVID cast uncertainties to the efficacy of vaccines. If the virus mutates to strains insensitive to a vaccine, the brand needs to be modified frequently. Again it is not fully clear whether coronavirus exposure provides long lasting immunity, because COVID is a new disease with a history of about 5 months. Present evidence points to an immunity least up to this period of time. Although a vaccine giving short term immunity cannot eradicate COVID, it would limit the spread and reduce the severity of the disease.

Even if contraction of COVID doesn’t provide long lasting immunity, there is no a priori reason to rule out vaccines capable of providing life time protection – but a long way to go.

Coronavirus disease might sometimes fade away on its own. Or human scientific ingenuity will eventually rid world of this malady. The question is the time frame and the adjustments we need to adopt until one of the above eventualities happen.

Writer Prof.Kirthi Tennakone, National Institute of Fundamental Studies can be reached via email: ktenna@yahoo.co.uk