A. Introduction:
In the late 18th century, Edward Jenner pioneered what immunologists refer to as “active immunization,” a process in which administering an antigen stimulates the host immune system to produce antibodies, along with B and T cells. This enables the immune system to mount an immediate response upon subsequent exposure to the same antigen, effectively preventing its progression and either attenuating or eliminating the disease. This groundbreaking work marked the birth of active immunization, paving the way for the emergence of vaccinology and a legacy shaped by countless remarkable scientists whose discoveries have defined modern immunization.
Since the World Health Organization (WHO)’s declaration of smallpox eradication in 1980, two more viruses were declared eradicated – polio 2 in 2015 and polio 3 in 2019. mainly because of the implementation of immunization programs which include cornerstone vaccines but beyond that can differ regionally.
The first Expanded Programme on Immunization (EPI) was established by the World Health Assembly in May 1974, demonstrating a proactive commitment to extending the protective benefits of vaccination globally. Inspired by the success of the smallpox eradication campaign WHO launched this collaborative initiative with the initial goal of vaccinating all children against seven major diseases: smallpox, tuberculosis, diphtheria, tetanus, pertussis, poliomyelitis, and measles by 1990.
Over time, the EPI has expanded to include vaccines targeting additional global and region-specific pathogens and expanded to age groups beyond infancy, with decisions on inclusion made by individual country programs. Since its inception, the programme has seen remarkable growth in the number of diseases covered, supported by catalytic strategies, innovative initiatives, and a unified global vision. This expansion has resulted in significant increases in both the breadth of protection and vaccine coverage.
Global coverage with the third dose of the diphtheria–tetanus–pertussis (DTP3) vaccine—commonly used as a proxy for vaccine program performance—rose from less than 5% in 1974 to 86% in 2019, prior to the COVID-19 pandemic.
Between 1974 and 2024, vaccination is estimated to have prevented 154 million deaths, including 146 million among children under the age of 5, of which 101 million were infants under 1 year old. Additionally, during this 50-year period, vaccination has contributed to the gain of 9 billion life-years and 10.2 billion years of full health. These achievements position vaccines and immunization as one of the most impactful healthcare interventions, second only, perhaps, to access to potable water (see Figures 1, 2, and 3).
(Data obtained from Shattock AJ, et al. Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. Lancet 2024; 403: 2307–16. https://doi.org/10.1016/).
B. The Long and Multifaceted Journey:
The following outlines a chronological sequence of achievements aimed at accomplishing the goals just described:
1. 1974: The 27th World Health Assembly: Formally established EPI against diphtheria, pertussis, tetanus, measles, poliomyelitis, tuberculosis, smallpox, and other diseases, where applicable, according to country-specific epidemiological situation.
2. 1979: Pan American Health Organization (PAHO): The resolution of the Pan American Sanitary Conference established the working capital for the PAHO Revolving Fund, a mechanism designed to facilitate pooled procurement and enhance access to vaccines, syringes, and cold-chain equipment at affordable prices.
3. 1982: UNICEF Child Survival and Development Revolution: The Child Survival and Development Revolution emphasized four key interventions: growth monitoring, oral rehydration therapy, promotion of breastfeeding, and immunization.
4. 1984: EPI’s first standardized schedule: Included were vaccinations for tuberculosis (BCG vaccine at birth); diphtheria, tetanus, and pertussis (DTP); poliomyelitis (administered alongside DTP at 6, 10, and 14 weeks); and measles (at 9 months).
5. 1990: Declaration of Manhattan, Children’s Vaccine Initiative: Its goal was to accelerate efforts to develop vaccines that would strengthen and enhance the effectiveness of the Expanded Programme on Immunization (EPI).
6. 1999: The Strategic Advisory Group of Experts (SAGE) on immunization: A vital arm of the WHO dedicated to global vaccine-related policies, recommendations, prequalification, strategies, research and development (R&D), and addressing various aspects of vaccine-preventable diseases.
7. 2000: Gavi, The Vaccine Alliance: The “Vaccine Alliance”, a combined private-public partnership to make vaccines more affordable to developing countries, an essential tool for equity. In nearly 25 years since its launch, Gavi has made significant strides in advancing equity in vaccine manufacturing. In 2000, four of its five vaccine suppliers were based in wealthy countries. Today, the majority of its approximately 20 suppliers are located in developing countries. Gavi has created a marketplace for large-scale, low-cost manufacturing in countries like India, Brazil, China, Indonesia, and others.
8. 2000 to present: ongoing acceleration of new vaccine production and implementation:
– The Meningitis Vaccine Project facilitated the development, testing, licensure, and introduction of the meningococcal A conjugate vaccine for the meningitis belt in Africa.
– The Accelerated Development and Introduction Plans for pneumococcal conjugate vaccines (PCV) and rotavirus vaccines, along with the Haemophilus influenzae type B Initiative, significantly expedited vaccine introduction in Gavi-supported countries.
– The Malaria Vaccine Implementation Programme.
9. 2017: Coalition for Epidemic Preparedness Innovations (CEPI)
As a global response to Ebola virus, Zika virus, and severe acute respiratory syndrome (known as SARS) outbreaks, CEPI was launched to develop safe and effective vaccines for emerging infectious diseases to prevent future epidemics. Currently CEPI plays a vital role in accelerating vaccine implementation during outbreaks, epidemics, and pandemics, as demonstrated by initiatives such as the “100-Day Mission for Pandemic Vaccine Implementation.”
10. 2020–23: COVID-19 Vaccines Global Access (COVAX): COVAX was the vaccine mainstem created to accelerate the development, production, and equitable distribution of COVID-19 tests, treatments, and vaccines. Its goal was to reduce COVID-19 mortality and severe disease, while facilitating the full restoration of societal and economic activity.
11. Others, but not less important:
- 2023–24: “The Big Catch-Up”
- EPI expansion
- The Global Polio Eradication -Initiative”
- Maternal and Neonatal Tetanus Elimination
- The Measles and Rubella Initiative
- The End TB strategy
- The Global Health Sector Strategy on Viral Hepatitis
- The Global Technical Strategy for Malaria
- The Eliminate Yellow Fever Epidemics Strategy
- The Global Strategy to Accelerate the Elimination of Cervical Cancer
- The Global Roadmap to Defeat Meningitis
C. A collaborative effort between the private and public sectors:
When Simón Bolívar, the great general who liberated much of South America from Spanish rule, was studying to become a military leader, his professor asked him, “What is the most important tool to start an army?” Bolívar replied, “Strategy.” His professor corrected him, saying, “No, money.”
WHO, Gavi, UNICEF, the Gates Foundation, Wellcome Trust, PATH, Rotary, the International Vaccine Institute, CEPI, Clinton Health Access Initiative, GSI, the World Bank, and other organizations, along with governments, have collaborated to leverage vaccines as a powerful tool in combating disease and addressing health disparities.
D. Task Priorities:
The WHO Immunization Agenda 2030 (IA2030) has established a structured approach to prioritize vaccine R&D for endemic pathogens based on regional and country-specific health needs. Through surveys conducted with policymakers and immunization stakeholders across WHO regions, eight criteria were used to assess pathogens, with two—annual deaths in children under five and contribution to antimicrobial resistance—emerging as top priorities in five of the six regions.
The survey responses revealed that these priority criteria did not significantly vary by region, demographic background, or expertise area of respondents. This consistency helped identify five pathogens—Mycobacterium tuberculosis, HIV-1, Klebsiella pneumoniae, Staphylococcus aureus, and extra-intestinal pathogenic Escherichia coli—as shared priorities across all regions. Additionally, six pathogens were uniquely prioritized in individual regions, reflecting localized health needs.
By merging the top ten pathogen lists from each region, WHO derived a global priority list of 17 pathogens for targeted vaccine R&D. To support this agenda, 34 distinct R&D use cases were identified, divided into categories based on necessary actions: Advance product development (the majority), Research, and Prepare to implement. This categorization helps streamline efforts to accelerate vaccine development and implementation for priority pathogens globally.
The following are the 17 global priority pathogens for targeted vaccine R&D:
- Plasmodium falciparum (Malaria)
- Norovirus
- Non Typhoidal Salmonella
- Leishmania species
- Group B Streptococcus
- Dengue virus
- Influenza virus
- Cytomegalovirus
- Shigella species
- Respiratory Syncytial Virus
- Hepatitis C virus
- Group A Streptococcus
- Staphylococcus aureus
- Mycobacterium tuberculosis
- Klebsiella pneumoniae
- HIV-1
- Extra-intestinal pathogenic Escherichia coli
E. Conclusions:
It is impossible to fully conclude such a multifaceted effort, where, despite significant achievements, there is still much to be done. In our view, scientific leaders must collaborate with their counterparts in the financial and political sectors. Without this partnership, the substantial disparities in vaccine access and implementation will persist, preventing a net global meaningful progress. First and foremost, there is no comparison between the investment in war and weapons and the investment in preventive medicine.
We acknowledge Prof. Ralf Clemens for both his input and feedback in this section.
