Two centuries of vaccination: historical and conceptual approach and future perspectives

Abstract

Over the past two centuries, vaccines have been critical for the prevention of infectious diseases and are considered milestones in the medical and public health history. The World Health Organization estimates that vaccination currently prevents approximately 3.5-5 million deaths annually, attributed to diseases such as diphtheria, tetanus, pertussis, influenza, and measles. Vaccination has been instrumental in eradicating important pathogens, including the smallpox virus and wild poliovirus types 2 and 3. This narrative review offers a detailed journey through the history and advancements in vaccinology, tailored for healthcare workers. It traces pivotal milestones, beginning with the variolation practices in the early 17th century, the development of the first smallpox vaccine, and the continuous evolution and innovation in vaccine development up to the present day. We also briefly review immunological principles underlying vaccination, as well as the main vaccine types, with a special mention of the recently introduced mRNA vaccine technology. Additionally, we discuss the broad benefits of vaccines, including their role in reducing morbidity and mortality, and in fostering socioeconomic development in communities. Finally, we address the issue of vaccine hesitancy and discuss effective strategies to promote vaccine acceptance. Research, collaboration, and the widespread acceptance and use of vaccines are imperative for the continued success of vaccination programs in controlling and ultimately eradicating infectious diseases.

Keywords: health literacy; history of vaccines; types of vaccines; vaccine development; vaccine hesitancy; vaccines; vaccinology.

Figure 1

Immune response to vaccination and acquisition of immunity. (A) Immune response post-vaccination. This process is initiated by the activation of innate immune cells including macrophages and dendritic cells, which engulf and process antigens, leading to the presentation of antigenic peptides (epitopes) via class I or II major histocompatibility complex (MHC-I or MHC-II). These activated innate cells present antigens to CD4 and CD8 T lymphocytes, leading to their activation. Once activated, these T cells proliferate and exercise their effector functions; notably, CD4 T cells stimulate B lymphocytes specific to the antigen. These B cells proliferate and mature into plasma cells, producing antigen-specific antibodies. Of note, a number of memory T and B cells persist in the body to provide long-term immunity. Also, plasma cells can become long-lived plasma cells and secrete antibodies for months or years. (B) Timeline of antibody production post-vaccination. Primary and secondary immune responses are shown following the initial vaccination and subsequent booster dose, respectively. These generated antibodies and memory cells provide protective immunity against future exposure to the target pathogen. This figure was created using BioRender.com.

Figure 2

General description of the vaccine development pipeline. The process of designing, developing, and testing a vaccine involves a series of steps. It begins with the Research and development stage, where potential vaccine candidates are identified. Subsequently, preclinical studies with animals are carried out to evaluate the efficacy and safety of the vaccine candidates. The process advances to the Clinical Studies stage after a successful proof of concept of the vaccine candidate. This stage is divided into Phase I (safety and dosing), Phase II (efficacy and side effects), and Phase III (monitoring for adverse reactions in a larger population) trials. Upon successful completion of these clinical trials, the process moves to the Post-Manufacturing Approval and Phase IV, surveillance studies. Here, vaccines undergo a strict approval process to receive regulatory sanction for public use, along with ongoing surveillance to track long-term effectiveness and possible side effects. The main activities within each stage are detailed. This figure was created using BioRender.com.

Figure 3

Main types of vaccines. (A) Live attenuated vaccines use a weakened form of the pathogen. (B) Inactivated vaccines contain a killed version of the pathogen, with surface antigens intact but the genome inactivated. (C) Subunit vaccines include only selected antigens from the pathogen. (D) Vector-based vaccines use a harmless vector to carry a fragment of the genome of the target pathogen. (E) Nucleic acid vaccines use the genetic material from the pathogen, either DNA or RNA, encapsulated within a delivery mechanism, such as liposomes or introduced through electroporation (DNA). All these types of vaccines aim to stimulate the immune response to a specific pathogen, although they may have different mechanisms of action. This figure was created using BioRender.com.

Figure 4

Global impact of vaccination on selected infectious diseases (1980–2021). This figure illustrates the number of reported cases for selected vaccine-preventable diseases (VPDs), including Diphtheria (A), Tetanus (B), Pertussis (C), Polio (D), Measles (E), and Rubella (F), from 1980 through 2021. The data was submitted to the World Health Organization (WHO) annually via the WHO/UNICEF Joint Reporting Form on Immunization (JRF). The most recent WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) for these specific VPDs on a global scale are presented. Notably, the increase in vaccination coverage led to a marked decrease in the number of cases reported annually for each of these diseases. Data were sourced from the World Health Organization's immunization data portal, accessible at: https://immunizationdata.who.int/.

Figure 5

Multifaceted approach to mitigate vaccine hesitancy. Diagnostic tools, such as surveys, can be utilized to identify potential barriers to vaccination. Building trust necessitates an active approach to addressing public concerns, misconceptions, and fears, while advocating for “radical transparency” in science communication. To ensure effective communication about vaccines, comprehensive campaigns targeting both the general population and specific groups and communities are imperative. Enhancing communication between healthcare workers and patients is key, requiring the adoption of presumptive language and motivational interviewing techniques to build trust and facilitate informed decision-making. Vaccine advocates, including community leaders and healthcare workers, play a crucial role. Programs that engage parents as active participants are equally significant. In the digital age, infoveillance is crucial for monitor trends on social media platforms and counteracting misinformation and disinformation about vaccines. Lastly, while coercive strategies, such as vaccination mandates and financial incentives can be effective, their implementation must be judiciously considered and culturally and regionally adapted. PACV, parent attitudes about childhood vaccines. BeSD, behavioral and social drivers of vaccine uptake model. This figure was created using BioRender.com.