This piece of work in its final form had its own share of emotional strain and personal sacrifices. The journey of compiling, researching and articulating the immense complexities of vaccinology demanded a relentless focus that was both intellectually demanding and emotionally taxing. In a world grappled with misinformation and inequity, there were moments of profound self-doubt and pressure, particularly in navigating the ethical and societal dimensions. The responsibility to capture the weight of global health challenges, alongside the inspiring stories of innovation and resilience, often were overwhelming. Yet, the desire to better understanding this critical field was the driving force, providing the determination needed to persevere through the process. All in all, the objective was to provide a 360º view of the world of vaccinology as it has evolved with time. Immunisation strategies have revolutionised public healthcare significantly, reducing the burden of infectious diseases and saving millions of lives worldwide. Being able to contain pathogenic diseases that were earlier unpreventable, vaccines have fundamentally redefined the threats of infectious diseases towards humanity. This piece of work compiles the multifaceted realm of vaccinology, thoroughly exploring its genesis, contemporary advancements and future directions. It details the evolution of vaccine science from early variolation practices to the sophisticated molecular platforms including that of the mRNA, emphasising the critical role of bioprocess engineering in scaling-up vaccine production to meet the increasing global demand. Driven by the emerging and reemerging infectious diseases as global pandemics and challenges to ensure equitable healthcare, the importance of vaccinology research is paramount. Advancements in bioprocess technologies and artificial intelligence (AI) have revolutionised vaccine development and its large-scale production, highlighting the need for sustained research collaboration to address global health challenges. Integration of reverse vaccinology powered by AI and machine learning (ML) further accelerates the efforts, opening new avenues in combating emerging pathogens rapidly and effectively. This work explores not only the technical aspects of vaccine science but also the societal, ethical and policy dimensions that influence vaccination efforts.

This chapter attempts to travel the timeline and dissect historical perspectives of vaccination. Vaccine that protects and shields from numerous dangerous diseases (vaccine-preventable diseases; VPD) is an important area of research and development. Considering that vaccine has been very useful in successfully combating numerous infectious diseases in the past 200 years, they are considered as a historical turning point in the field of public health and medicines. Critical illnesses like the smallpox and wild polio (virus types 2 and 3) have mostly been eradicated as a result of mass immunisation programmes worldwide. Research, collaboration and widespread vaccination campaigns were necessary in vaccination efforts to control and ultimately eradicate infectious diseases. Biotechnological research has progressed to a level where producing recombinant vaccines is feasible. Research and development efforts on therapeutic vaccines are ongoing. Vaccine research in recombinant DNA/RNA technologies and therapeutic vaccinations for specific illnesses seem to be the future. This article offers a comprehensive history of vaccination since inception to its present forms, with future projections. Beginning with the variolation techniques in the early 17th century, it discusses the important turn of events from its discovery to the continued advancements and inventions till the covid-19 vaccine. Alongside the detailed core aspect, the chapter also describes the benefits of the one health approach with the zoonotic diseases in focus.

The process of vaccine development involves numerous stages from research, discovery, innovation, formulation, testing, mass production, logistics, deployment and administering the vaccine to the target population. The COVID-19 pandemic expedited the endeavour to develop vaccine worldwide that is unparalleled in history. In addition to the steps that were similar during the usual vaccine development process, it called for stronger collaborative teamwork with stricter deadlines during the pandemic due to the emergency situation that built up everywhere (in its spread as well as severity). Research was expedited, potential candidate vaccines were discovered and the proofs of concept were designed that paved the way for pre-clinical efficacy testing. Multiple-step clinical trials to ascertain that the vaccines were effective and safe at least for ‘emergency use’ in human subjects were carried out swiftly. The emergency usage regulatory approval and recommending the usage pattern involved accelerated review procedures. It immediately followed rapid scaling-up for increased production in order to meet the need to save as many human lives as possible across the globe. The approved vaccines were simultaneously evaluated for safety through dedicated pharmacovigilance systems. The future of vaccine development shall also focus on improving the worldwide access to vaccines, managing the virus variants and streamlining mass vaccination campaigns. Comprehending the research, development and administration phases to create and implement life saving vaccinations within the regulatory framework amid international health emergencies as encountered during the COVID-19 pandemic and the enormous collective endeavours are highlighted in this chapter.

Messenger RNA (mRNA) vaccine was the first authorised vaccine developed using mRNA vaccine production technology, against SARS-CoV-2. Well accepted by the population, it proved to be a major life saving intervention during the COVID-19 pandemic. This article discusses the mRNA vaccine technology and its major advantages, and provides an update on the various ongoing and completed clinical trials on the leading mRNA vaccines against various viral diseases. It also delves into the prospects and the technical challenges associated with the manufacturing of mRNA vaccine and the issues with its deployment in the low- and middle-income countries around the world. Despite the already available classical vaccine candidates, the persistent interest and continuous research in mRNA vaccine technology and the related storage, immunogenicity and lipid nanoparticles delivery aspects have helped in expanding and upgrading the vaccinology arsenals to counter diseases. The technology holds promises in opening new vistas to protect against infectious diseases and the associated complications, where safe and effective immunisations are currently lacking. Furthermore, as mRNA vaccines evolve, they offer new hope against neglected and reemerging diseases like rabies, Zika, and Nipah viruses. The flexibility and rapid adaptability of this platform underscore its potential to address unmet medical needs, laying the groundwork for universal and multi-pathogen vaccines, vital in averting future pandemics. Enhanced by advancements in nanotechnology and innovative delivery systems, mRNA vaccines are poised to revolutionise infectious disease prevention, cancer treatment, and genetic disorders, marking a new era in vaccinology and offering hope for global health challenges through continued investment in research and infrastructure.

Constantly emerging and reemerging vaccine-preventable infectious diseases recently around the globe challenged the health infrastructure and has been a critical concern for the medical fraternity. There are 21 other neglected tropical diseases, as classified and recently updated by the World Health Organisation, many of which are seemingly vaccine-preventable. The unprecedented scenario that the world encountered during the recent COVID-19 pandemic was also a ‘silver lining in the dark cloud’ for primarily the vaccinologists. The scientific world witnessed stupendous developments in vaccine development. One such instance was the cutting-edge mRNA vaccine development platform. Once a vaccine is successfully designed, the next step is scaling it up in a milieu that is conducive for its mass production. There are numerous ways to achieve it, from biological system (animal models like the chick embryo, mouse cell-lines, suspension-cultured tobacco cells) to the non-biological (bioreactor) settings. This chapter provides a comprehensive overview of the intricacies in vaccine development, from designing to large-scale manufacturing (mass production). It delves into key scientific guiding principles behind developing and formulating vaccines, adopting both the traditional and emerging bioprocessing and bioseparation engineering and technology. It also explores the technical and management challenges faced before and during scaling up, including maintaining product efficacy, ensuring high quality for human administration, and navigating regulatory landscapes, among others. The chapter offers a holistic understanding of bioprocessing continuum, to educate and inform the research (academia) and development (bioindustry) community for more promising and effective strategies in the future to optimise vaccine production, thus contributing to the global public healthcare initiatives.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the global COVID-19 (coronavirus disease 2019) pandemic has claimed a considerable number of lives worldwide. The unanticipated global spread of SARS CoV-2 has resulted in serious issues within the medical systems and healthcare facilities. Creating efficient vaccines against the virus, even after all of efforts, has been on high priority and is time-taking due to the frequent mutations. A critical stage in vaccine development is figuring out the potential antigen. As a ground breaking technique introduced in 2000, Reverse vaccinology (RV) reduces the required time considerably from 5–15 years to 1–2 years in identifying antigens. Various RV tools are powered by big-data analytics, artificial intelligence (AI) and machine learning (ML) techniques. AI and ML models have demonstrated their potentials in expediting the identification and refinement of novel antivirals or potent vaccination candidates. By utilising datasets available through several dedicated databases, it is more beneficial in identifying current medications that inhibit the human Coronavirus and next-gen healthcare possibilities.

Recent pandemic (COVID-19) impacted global economy significantly and increased economic disparity. Vaccines are significantly beneficial and cost effective compared to other public healthcare preventives. Vaccines reduce hospitalisation, treatment costs and associated morbidity and mortality. Although COVID-19 vaccination and natural viral infection protected against reinfection, it waned in part due to emerging novel variants. Waning immunity from vaccine and natural infection are documented, and it was more so in severe hospitalised COVID-19. Many countries developed their own vaccines successfully to counter as COVID-19 became global. Vaccines needed updates to effectively fight COVID-19 as the wild strain constantly mutated. Among the intrinsic, perinatal, extrinsic, environmental, behavioural and nutritional aspects, the host factors included antibiotics usage pattern, sleep habits, physical activities, smoking habit and alcohol intake. Similarly, the external factors influencing vaccine response included childhood vaccination, early-age infections, nutrient supplements soon after birth, and breastfeeding pattern. Vaccination time also affected the efficacy. Forenoon vaccination developed less breakthrough infection compared to afternoon or evening vaccination due to varying immunological responses like immune cell functions, recruitment and transport, owing to circadian rhythm. Although vaccination side-effects are there, almost all vaccines are reportedly safe, effective and prevented serious illness, hospitalisation and death. Vaccine usually takes two weeks to manifest, and it prevented 14·4–19.8 million pandemic fatalities globally in 185 nations in a single year during December 2020 and December 2021. It was necessary that the boosters alongside vaccines enhanced immunological effects and provided extended protection. Thus, vaccine and booster design and development, dosing, targeted immunisation, cost-efficacy and vaccine acceptance are challenges to address. Government, not-for-profit organisations, health agencies and researchers may systematically analyse, justify and validate vaccine R&D and vaccinations economics. This chapter comprehends biological, commercial and economic benefits and impacts of booster dose in vaccination drives, and the roadmap ahead.

The world turned into a grossly inhabitable during the infamous COVID-19 pandemic, with community health issues everywhere. Each one felt unsafe if other earthly inhabitants were, be it humans or other living beings. Onset of SARS CoV-2 set a ‘new normal’ world order. The ever-evolving and mutating SARS CoV-2 variants extended the pandemic wave after wave thereby complicating the situation, pushing the global healthcare system to its limits and exposing its underbelly. The continually evolving variants were more aggressively transmissive and infective. As the world still reels under tremendous healthcare pressure, other infectious diseases are emerging as are identified by the World Health Organisation (WHO), creating international health emergency situations. The situation becomes alarming with the increasing zoonotic (spillover) and reverse zoonotic (spillback) factors being more proactive in the disease spread. There is a greater need to vaccinate not only humans but also animals, especially the domesticated ones and known reservoirs/carriers. Vaccines must be developed on priority and equitably distributed as the first step to counter a pandemic or potential pandemic. Vaccination is self-limiting due to increasing reported breakthrough infection cases. A strong link of the environmental health to the overall global health needs to be acknowledged, and due diligent measures taken. Hence, there is a strong need of the One Health approach as a 360° solution, and follow it up at global-scale both in letter and spirit. This chapter discusses spillover and spillback of diseases like SARS-CoV-2 and Mpox as case examples, the mitigation strategies and the need for workable One Health models, and challenges and measures to counter future outbreaks. It stresses on foolproof vaccination strategies across to catalyse individual and herd immunities for universal wellbeing.

The world turned into a grossly inhabitable during the infamous COVID-19 pandemic, with community health issues everywhere. Each one felt unsafe if other earthly inhabitants were, be it humans or other living beings. Onset of SARS CoV-2 set a ‘new normal’ world order. The ever-evolving and mutating SARS CoV-2 variants extended the pandemic wave after wave thereby complicating the situation, pushing the global healthcare system to its limits and exposing its underbelly. The continually evolving variants were more aggressively transmissive and infective. As the world still reels under tremendous healthcare pressure, other infectious diseases are emerging as are identified by the World Health Organisation (WHO), creating international health emergency situations. The situation becomes alarming with the increasing zoonotic (spillover) and reverse zoonotic (spillback) factors being more proactive in the disease spread. There is a greater need to vaccinate not only humans but also animals, especially the domesticated ones and known reservoirs/carriers. Vaccines must be developed on priority and equitably distributed as the first step to counter a pandemic or potential pandemic. Vaccination is self-limiting due to increasing reported breakthrough infection cases. A strong link of the environmental health to the overall global health needs to be acknowledged, and due diligent measures taken. Hence, there is a strong need of the One Health approach as a 360° solution, and follow it up at global-scale both in letter and spirit. This chapter discusses spillover and spillback of diseases like SARS-CoV-2 and Mpox as case examples, the mitigation strategies and the need for workable One Health models, and challenges and measures to counter future outbreaks. It stresses on foolproof vaccination strategies across to catalyse individual and herd immunities for universal wellbeing.

The pandemic in 2019-2022 spread swiftly and became global in no time, caused by SARS-CoV-2. Vaccines were rapidly developed against the virus to restore public health and save global economy. Vaccines for immunisation drives were developed in a year of the pandemic becoming global and approved for ‘emergency use’ following expeditious development protocols. Vaccine development employed numerous nucleic acid, adenovirus and protein-based state-of-art molecular platforms, alongside the conventional attenuated and inactivated virus approaches. The majority of the attempts were successful and approved for use. All the approved vaccines were found safe and effective as per Phase I through Phase III clinical trials’ results. Mass immunisation drives demonstrably led to reduced hospitalisation, low disease severity and less mortality. Yet, there were initial vaccination hesitation across the world due to associated safety concerns about its possible long-term negative consequences. A part of it was attributed to technical reasons (as clinical trials were not fully complete with sturdy and convincing outcomes), and a majority was due to the misinformation that floated on the social media and other digital communications. Vaccine deployment across the globe was far from being equitable. Thus, immunisation was rapid in higher income (developed) nations with access to innovative advanced vaccines while low immunisation rates were seen in the low- and medium-income countries accessing majorly the vaccines based on simple technology. Given the scale and spread of the pandemic, scaled-up vaccine production and equitable distribution to limit viral spread and improve global health and socioeconomy were critical. This chapter attempts to dissect these scenarios and lessons learnt from these to prepare better for any such pandemic in future.

A Ace2 receptor 159, 172 Adjuvant 9, 13, 43, 48, 50, 51, 62, 66, 166, 167, 240, 302 Adjuvants 3, 5, 9, 13, 50, 89, 110, 116, 138, 139, 171, 194, 207, 299, 303 Adverse event 57, 59 Animal model 46, 60, 62 Antibody 5, 18, 19, 39, 40, 44, 47, 70, 74, 78, 79, 80, 81, 82, 88, 93, 94, 95, 106, 108, 139, 158, 162, 177, 185, 188, 195, 196, 197, 203, 206, 207, 298, 299, 304 Antigen 5, 8, 9, 10, 12, 18, 22, 36, 38, 39, 40, 43, 44, 48, 49, 72, 75, 79, 81, 83, 84, 85, 91, 98, 102, 103, 107, 108, 109, 110, 115, 116, 117, 124, 125, 138, 139, 140, 141, 151, 163, 164, 165, 166, 180, 195, 196, 204, 207, 229, 300, 303, 304, 305