Vaccines are versatile, valuable and vital

More than 1,000 years ago people in India and China protected themselves from smallpox with one of the earliest known practices of inoculation by rubbing the powdered scab from an infected patient into a cut in the skin of a healthy person. This gave protection from disease in some people, but it also spread the disease in others, sometimes fatally.

The story of Edward Jenner, who observed the smooth skin of milkmaids and translated that knowledge into using cowpox to protect against smallpox, is well known, and it is this discovery that laid the foundation for the creation of modern vaccines.

Until the 20th century, no-one recognised that cowpox and smallpox were caused by viruses, or that inducing protection against one resulted in protection from the other, a phenomenon known as cross-reactivity or cross-protection.

While the effectiveness and safety of vaccines is proven beyond doubt, new challenges have emerged, from falling vaccination rates in developing countries, to the anti-vaccine movement in the West.

The production and use of vaccines came of age in the 20th, resulting in the World Health Organization’s estimate that vaccines save 2.5 million lives every year. In the 1960s and 1970s, Maurice Hilleman, a vaccinologist, developed more than 40 vaccines and is credited with saving more lives than any other medical scientist in history.

Most vaccines are made using traditional means of weakening or killing the whole organism, (attenuated or dead vaccines) and technological advances have ensured mass production and supply across the world.

Measles vaccines alone have prevented an estimated 20.4 million deaths from 2000 to 2016. Vaccines are undoubtedly the most cost-effective solution to prevent diseases and provide the best returns on investment in public health, protecting not just those who receive them, but curtailing infection rates with community uptake. This phenomenon, known as herd immunity or herd protection, may eventually help eradicate many previously dreaded pathogens.

Challenges in making vaccines

Smallpox was the first human disease to be eradicated from the world, because a good vaccine was used effectively. Polio was identified as the next target, and the world is on the verge of becoming free of polio — again a goal being achieved through prevention of infection.

However, not all diseases are amenable to easy vaccine development. Viral targets have been simpler than bacteria, and diseases such as malaria, dengue, tuberculosis and AIDS are likely to remain a major vaccine hurdle for many years. Most existing vaccines were created using traditional approaches, however, as we enter the phase of developing vaccines for complex pathogens/diseases — such as dengue virus, different influenza virus strains, tuberculosis, and AIDS — there is a need to adopt novel and smart approaches.

The development of vaccines is a long and hard road, requiring many years and stages of assessment; first in animals (pre-clinical toxicity), then in humans (phase 1), the ability to induce an immune response (phase 2) and for protection from disease (phase 3), as well as standardization of the manufacturing process for complex biological material.

Challenges in vaccines come from the complexity of the organism or the complexity of the response to the vaccine. Almost 100 years since the development of the Bacille Calmette-Guérin (BCG) vaccine, we have not been successful in either combating tuberculosis (TB) or developing a vaccine that is more effective than BCG. Nevertheless, more than a dozen potential vaccine candidates for TB are at different phases of evaluation.

There is an urgent need to supplement these vaccine development efforts with relevant and reliable information on biomarkers of disease or those that predict protection.

AIDS vaccine development has suffered serious setbacks, with some of the most promising candidates failing at late stages of testing. However, failed attempts have provided insights into human immune response to HIV, which have propelled efforts towards better strategies and partnerships. Similarly, studies using controlled human infection models are providing evidence for a better malaria and dengue vaccines. For new and effective vaccines, new partnerships are needed, involving disease biologists, vaccine developers, epidemiologists and clinician researchers.

Despite best efforts of various countries and multi-lateral agencies, one in 10 infants did not receive any vaccines in 2016.

Furthermore, a wide gap in resources, geopolitical stability and population distribution has resulted in disproportionate vaccine coverage rates across the world. In addition, coverage rates vary for different vaccines. Global vaccine coverage has remained stagnant at 86 per cent for the vaccines covered under the universal immunization programs, and vaccine coverage for some of the newly introduced vaccines, such as rotavirus is barely 25 per cent. The Global Vaccine Action Plan (GVAP) had set lofty goals of equitable access to vaccines by 2020, but only one of the goals is on track. 73 per cent of the world’s poorest people are in low-and middle-income countries (LMICs) and delivering vaccines to these resource-poor settings must be a global priority.

The establishment and sustenance of the Gavi Alliance has been a game-changer over the past 15 years, supporting LMICs to introduce new vaccines and improve their immunisation programmes. The logistics of getting vaccines to certain countries and keeping them in appropriate storage is also a challenge. For example, because vaccines need to be kept cold, a purpose-built cold chain points distribution system needed to be created in India.

Vaccines avert disease and death, but when diseases disappear, people become complacent or discount the value of vaccines. Anti-vaccine lobbyists count on respite from the disease to highlight fears about the side-effects of vaccines — some real but rare — and others, such as the autism link to the MMR vaccine, untrue and disproved. These messages can significantly impact vaccine coverage rates, and, as in the cases of measles, cause outbreaks through unvaccinated and vulnerable children.

Despite vaccines being developed and available for several decades, many people at risk do not get them. Brazil is dealing with more than 1,000 cases of yellow fever.

Close to 60 countries are endemic for yellow fever, with an estimated at-risk population of one billion. Yellow fever vaccine was the first successful vaccine developed against a human virus, in 1938, however the supply of vaccine has not kept pace with the disease. This is because vaccines, as public health interventions, need to be cheap and affordable. India’s vaccine companies, which produce millions of doses of vaccines every day, supply the global south with this essential tool for prevention.

Vaccines are vital for prevention of disease and have been a success story. India’s contribution to public health vaccines has been enormous. However, most vaccines made in India are high-volume and low cost, based on technologies that were developed elsewhere.

In order to make new and innovative vaccines and to use them, we need a focused investment in research and development, with partnerships between academia, industry and government, backed by a scientifically educated population which recognizes the value and benefits of prevention.

(The authors are from the Translational Health Science and Technology Institute, Faridabad, India)

[Nature India Custom Edition: Decade of Discovery]