JVR_2025v15n1

Journal of Vaccine Research 2025, Vol.15 http://medscipublisher.com/index.php/jvr © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.

Journal of Vaccine Research 2025, Vol.15 http://medscipublisher.com/index.php/jvr © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. MedSci Publisher is an international Open Access publisher specializing in veterinary vaccine, prophylactic vaccines, therapeutic vaccines, AIDS vaccines, clinical vaccines at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. Publisher MedSci Publisher Editedby Editorial Team of Journal of Vaccine Research Email: edit@jvr.medscipublisher.com Website: http://medscipublisher.com/index.php/jvr Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada Journal of Vaccine Research (ISSN 1927-6486) is an open access, peer reviewed journal published online by MedSciPublisher. The journal is considering all the latest and outstanding research articles, letters and reviews in all aspects of vaccine research, mainly interested in vaccines and vaccination research, immunologic testing including serology, cell-mediated immunity, cell culture, and cytokine assays, veterinary vaccine, prophylactic vaccines, therapeutic vaccines, AIDS vaccines and other clinical vaccines; vaccination research and methodology containing vaccine technology, vaccine adjuvants; as well as the expands field ofvaccines and vaccination research. All the articles published in Journal of Vaccine Research are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MedSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.

Journal of Vaccine Research (online), 2025, Vol. 15, No. 1 ISSN 1927-6486 http://medscipublisher.com/index.php/jvr © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content Comparative Analysis of Vaccination Strategies in Poultry Production Jinya Li, Qibin Xu Journal of Vaccine Research, 2025, Vol. 15, No. 1, 1-9 Factors Influencing Long-Term Vaccine-Induced Immunity JieZhang Journal of Vaccine Research, 2025, Vol. 15, No. 1, 10-22 HPV-Associated Oral Cancer: Case Reports and Implications for Vaccination Strategies Jianbang Chen Journal of Vaccine Research, 2025, Vol. 15, No. 1, 23-33 Vaccine Development for Vector-Borne Diseases: Case Studies and Challenges Tiantian Wang Journal of Vaccine Research, 2025, Vol. 15, No. 1, 34-44 Therapeutic Vaccines for Non-Small Cell Lung Cancer: Current Progress and Future Directions Jianmin Liu Journal of Vaccine Research, 2025, Vol. 15, No. 1, 45-55

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 1 Research Insight Open Access Comparative Analysis of Vaccination Strategies in Poultry Production Jinya Li, Qibin Xu Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: qinbin.xu@cuixi.org Journal of Vaccine Research, 2025, Vol.15, No.1 doi: 10.5376/jvr.2025.15.0001 Received: 10 Nov., 2024 Accepted: 15 Dec., 2024 Published: 02 Jan., 2025 Copyright © 2025 Li and Xu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li J.Y., and Xu Q.B., 2025, Comparative analysis of vaccination strategies in poultry production, Journal of Vaccine Research, 15(1): 1-9 (doi: 10.5376/jvr.2025.15.0001) Abstract This study explores the vaccination strategies in poultry farming, with emphasis on their roles in disease prevention, enhancing production capacity, and safeguarding public health. The types of vaccines are classified in this study, including attenuated live vaccines, inactivated vaccines, recombinant vaccines and nucleic acid vaccines. Their mechanisms of action, vaccination routes and targeted diseases, such as Newcastle disease and avian influenza, are also analyzed. This study further studies the strategic differences in vaccination timing, vaccination methods, and individual and large-scale vaccination approaches. The effectiveness is evaluated by considering the immune effect, feasibility and cost-effectiveness, while strictly examining problems such as antigen variation, biosafety risks and immunosuppression. Emerging technologies, such as RNA vaccines and precision immunization, are being explored as feasible solutions for future disease prevention and control. The conclusion of this review is to advocate a comprehensive strategy that combines vaccination with nutrition, genetics and policy support to achieve sustainable management of poultry health. Keywords Poultry vaccination; Vaccine strategies; Immunization technologies; Disease control in livestock; Cost-effectiveness 1 Introduction Vaccination is of vital importance in the health management of poultry and is a key means to prevent and control major infectious diseases that endanger the production and health of poultry flocks. The poultry farming industry, as an important source of global meat and egg supply, has always been threatened by pathogens such as viruses and bacteria. Vaccination is the main way to reduce the mortality and morbidity rates of poultry and minimize economic losses (Ravikumar et al., 2022). At present, there are various types of vaccines in use, such as attenuated live vaccines, inactivated vaccines, recombinant vector vaccines, subunit vaccines and virus-like particle vaccines (Garcia, 2017; Panting-Jackwood and Suarez, 2017; De Luca and Hess, 2024; Raji et al., 2024; Wang et al., 2024). These vaccines are of great significance for maintaining the health of poultry flocks, preventing the spread of diseases, and ensuring the sustainable development of poultry farming. The benefits of vaccination are not only about controlling diseases, but also have significant impacts on productivity, animal welfare and public health. Reasonable vaccination can reduce large-scale culling of poultry and the use of antibiotics, which not only improves animal welfare but also lowers economic losses (Azzouguen et al., 2020; Michel et al., 2023). At the same time, vaccination can also prevent zoonotic diseases, reduce virus transmission, ensure food safety and safeguard public health (Ravikumar et al., 2022; Astill et al., 2022). New vaccine technologies, such as virus-like particle vaccines and recombinant vector vaccines, have great potential in enhancing immune efficacy, ensuring safety, and achieving the distinction between infected and vaccinated animals, which is conducive to better disease surveillance and prevention and control (Pantin-Jackwood and Suarez, 2017; Wang et al., 2024; Gloanec et al., 2025). This study will comprehensively compare the current vaccination strategies in poultry farming, evaluate their effects, existing risks and future development trends. By summarizing the latest achievements and challenges in vaccine research and application, covering aspects such as vaccine types, vaccination methods, immune effects, and cost-benefits, it provides practical methods for poultry health management and also offers references for subsequent research and policy-making.

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 2 2 Types of Poultry Vaccines and Their Working Principles 2.1 Traditional vaccines: the use and differences of attenuated live vaccines and inactivated vaccines Attenuated live vaccines are made by reducing the pathogenicity of pathogens. Such vaccines can reproduce in poultry but will not cause diseases. This type of vaccine can stimulate a strong and long-lasting immune response in poultry by imitating the natural infection process. Generally, one dose can provide effective protection. In poultry farming, live attenuated vaccines are often used to prevent and control Newcastle disease, infectious bursal disease, etc. They can quickly make poultry immune and also stimulate humoral and cellular immunity (Bublot, 2023; Wang et al., 2024). Inactivated vaccines are made by killing pathogens to ensure that they can no longer reproduce. For poultry with weak immunity, inactivated vaccines are safer and there is no need to worry about them returning to a pathogenic state. However, usually multiple vaccinations are required, along with adjuvants, to enable the poultry to acquire sufficient immunity (Bublot, 2023; Feng et al., 2024). For diseases such as avian influenza, inactivated vaccines are commonly used for prevention and control. They have high safety. However, compared with live attenuated vaccines, sometimes the immune response they trigger is weaker and the duration is shorter (Pantin-Jackwood and Suarez, 2017; Bublot, 2023). 2.2 The development of recombinant vaccines, vector vaccines and nucleic acid (DNA/RNA) vaccines Recombinant vaccines and viral vector vaccines represent major breakthroughs in the field of poultry immunization. This type of vaccine uses harmless viruses, such as chickenpox virus or Turkey herpesvirus, as vectors and incorporates genes encoding protective antigens of the target pathogen, enabling poultry to be immune to multiple diseases simultaneously. They can be specifically designed to express specific antigens to facilitate the distinction between infected and vaccinated poultry, and can provide good protection even if there are maternal antibodies in the poultry (Romanutti et al., 2020; Hein et al., 2021; Wang et al., 2024). Nucleic acid vaccines include DNA vaccines and RNA vaccines. They directly deliver the genetic material encoding pathogen antigens into poultry cells, causing the cells to produce antigens and thereby triggering an immune response (Bublot, 2023). This type of vaccine has a fast development speed, high safety, and strong ability to stimulate cellular and humoral immunity. Virus-like particle (VLP) vaccines are another new technology. They have a similar appearance to viruses but no genetic material, providing a precise, safe and immunoeffective new option for the prevention and control of poultry diseases (Astill et al., 2022; Raji et al., 2024). 2.3 Take newcastle disease, avian influenza and infectious bursal disease as examples For the prevention and control of Newcastle disease, attenuated live vaccines and inactivated vaccines can be used. Recombinant vector vaccines can also enhance the protective effect and simplify the vaccination process (Hein et al., 2021). Which vaccine to choose specifically depends on factors such as the maternal antibody situation, the expected duration of immunity, and the risk of disease outbreak (Wang et al., 2024). The prevention and control of avian influenza has evolved from mainly using inactivated vaccines to the current adoption of recombinant vaccines and vector vaccines. These new vaccines are suitable for newly hatched chicks and also help distinguish infected and vaccinated poultry (Romanutti et al., 2020). The new type of vaccine has a remarkable effect in reducing the incidence of diseases in poultry and lowering the transmission of the virus, which is very helpful for safeguarding the health of poultry flocks and public health (Pantin-Jackwood and Suarez, 2017; Astill et al., 2022). Infectious bursal disease is mainly controlled by attenuated live vaccines, but nowadays recombinant vector vaccines are also increasingly used. They can solve problems such as interference of maternal antibodies and also enable poultry to obtain long-term immunity (Hein et al., 2021). The selection of vaccines should comprehensively consider the epidemic situation of the disease, safety, and whether extensive and long-lasting protection is needed (Romanutti et al., 2020; Wang et al., 2024).

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 3 3 Vaccination Strategies 3.1 Early vaccination, regular booster vaccination and emergency vaccination programs Vaccinating poultry in the early stages of their lives, including egg inoculation, is becoming increasingly common and can provide immunity to poultry either before or immediately after hatching. Compared with vaccinating after hatching, in-egg vaccination involves directly injecting the vaccine into the egg during hatching. This enables the chicks to grow better after hatching, enhances their immunity, and reduces the embryo mortality rate (Chao et al., 2019). This method is particularly useful for the prevention and control of Marek's disease and infectious bursal disease, because early protection is very crucial for the health of poultry flocks (Peebles, 2018). Regular booster vaccinations are crucial for maintaining the long-term immunity of poultry flocks, especially when they are constantly threatened by pathogens. The timing and frequency of booster shots should be determined based on different diseases, vaccine types and breeding models. They need to be carefully arranged so as to achieve the best immune effect and minimize protective loopholes (Soutter et al., 2020). When a disease breaks out, emergency vaccination needs to be initiated to quickly control the spread of the disease. This requires prompt action, usually through large-scale vaccination to protect susceptible poultry (Ravikumar et al., 2022). 3.2 Advantages and disadvantages of injection, drinking water and spray methods Injection vaccination, including intramuscular injection and subcutaneous injection, can ensure the accuracy of vaccine dosage and works well for some vaccines. However, this method is very labor-intensive and may cause stress or harm to poultry (Figure 1) (Peebles, 2018; Saeed et al., 2019). In commercial breeding, intramuscular injection can be operated through automated equipment to evenly vaccinate a large number of eggs before hatching. However, in large-scale flocks of poultry, it is relatively difficult to conduct injection and vaccination after hatching (Peebles, 2018). Figure 1 Application of in ovo technology for various biological supplements in poultry (Adopted from Saeed et al., 2019) Vaccinating poultry through drinking water and spraying is widely used in large-scale farming because it is convenient to operate and can quickly complete the vaccination of a large number of poultry (Renu et al., 2020; Ravikumar et al., 2022). Just like the Salmonella vaccine with chitosan adjuvant (Renu et al., 2020), when fed to poultry through drinking water or mixed feed, it can cause a strong immune response in the mucous membranes and the whole body of the poultry. However, these vaccination methods may result in different doses of vaccine

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 4 intake for each poultry, and the efficacy also depends on the feeding and drinking behaviors of the poultry, which may affect the efficacy of the vaccine (Renu et al., 2020; Jia et al., 2023). Spray and gel inoculation methods can enhance vaccine absorption and reduce stress in poultry, but careful operation is required to ensure that each poultry is evenly vaccinated. 3.3 Individual and large-scale vaccination: application scenarios in different production systems Individual vaccination, such as the injection method, is generally used in high-value breeding poultry or small-scale poultry flocks, because in such cases, it is relatively easy to precisely control the vaccine dosage and observe the vaccination effect (Peebles, 2018). This vaccination method can provide targeted protection and is suitable for those vaccines that require strict vaccination procedures or where large-scale vaccination is not very realistic. Large-scale vaccination methods, including drinking water, spraying and in-egg inoculation, are indispensable for large-scale commercial poultry farming and can efficiently vaccinate tens of thousands of poultry. These methods can reduce labor costs and the stress of poultry, and are very suitable for the breeding of broilers and laying hens. Whether to choose individual vaccination or large-scale vaccination depends on the size of the poultry flock, breeding goals, disease risks and existing resources. In intensive breeding, large-scale vaccination is more popular because it can flexibly expand the scale and is highly practical (Peebles, 2018; Saeed et al., 2019; Ravikumar et al., 2022). 4 Comparison of the Effectiveness of Vaccination Strategies 4.1 Protection rate, duration of immunity and adaptability to antigenic variations In poultry vaccination, the immune protection effects brought by different strategies are not the same. Compared with using only one type of vaccine, the combined use of attenuated live vaccines and inactivated booster vaccines, etc., usually enables poultry to produce higher antibody levels, stronger cellular immune responses, and better protective effects against diseases (Buharideen et al., 2021; Liu et al., 2022). The duration of immune protection is related to the type of vaccine and the timing of vaccination. For example, vaccinating poultry at hatcheries can make the immune level of the entire flock higher and more uniform. For viruses like avian influenza that are prone to mutation, in order for vaccines to adapt to antigen changes, it is necessary to update the vaccine strains regularly to ensure the protective effect (Figure 2) (Azzouguen et al., 2020; Ravikumar et al., 2022; Michel et al., 2023). Figure 2 Spatial distribution of the poultry population immunity against AI according to the different vaccination strategies (S) tested in the model (Adopted from Azzouguen et al., 2020) Nowadays, people are developing vaccines and new vaccination strategies that offer extensive protection, such as DNA primer/protein booster vaccines and recombinant vector vaccines, to address the issue of antigen variation and provide long-term cross-immune protection for poultry (Ravikumar et al., 2022; Liu et al., 2022). However,

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 5 the efficacy of these vaccines can be influenced by several factors, such as the situation of maternal antibodies in poultry, the matching degree between the vaccines and epidemic strains, and unified efficacy data are also needed to assist in the selection and use of appropriate vaccines (Meunier et al., 2015; Michel et al., 2023; Wang et al., 2024). 4.2 Equipment requirements, technical requirements, personnel training Whether the vaccination strategy can be smoothly implemented depends on the vaccination method and the breeding model. Vaccination in hatcheries, especially recombinant vaccines, is highly efficient and has a high vaccination rate, but it requires specialized equipment and professionally trained personnel to carry out in-egg vaccination or large-scale vaccination (Azzouguen et al., 2020; Wang et al., 2024). In contrast, when directly vaccinating poultry in farms, inactivated vaccines are generally used. This approach is more labor-intensive and time-consuming. Moreover, due to differences in vaccination operations, it is prone to cause inconsistent immune levels in poultry (Azzouguen et al., 2020; Michel et al., 2023). Large-scale vaccination through methods such as drinking water or spraying has been widely adopted because it is convenient to expand the vaccination range and can save labor costs. However, careful management is required to ensure that each poultry has uniform contact with and effective absorption of the vaccine (Ravikumar et al., 2022). Training the staff is crucial. This can reduce operational errors, ensure the correct use of vaccines, and maintain biosecurity, especially when using complex or new vaccine technologies (Wang et al., 2024; Bilal et al., 2025). 4.3 The economic benefits brought about by the reduction in vaccine costs and disease incidence rates Cost-benefit analysis shows that vaccination strategies for different poultry breeds and breeding types have the highest economic efficiency, and vaccination at hatcheries is usually more cost-effective than at breeding farms (Azzouguen et al., 2020). Vaccinating poultry can significantly reduce the prevalence and mortality rates, minimize related economic losses, and enhance the production efficiency and sustainability of the poultry farming industry (Ravikumar et al., 2022; Bilal et al., 2025). Although purchasing vaccines and equipment costs a lot of money at the beginning, the economic benefits brought about by the reduction of diseases, the improvement of poultry flock health, and the decrease in the demand for antibiotic use and poultry culling can offset these upfront costs. The most cost-effective vaccination strategy is to enable the entire poultry flock to obtain a high level of consistent immune protection, minimize difficulties in terms of manpower and transportation, and be able to be flexibly adjusted according to changes in disease threats (Azzouguen et al., 2020; Ravikumar et al., 2022; Bilal et al., 2025). 5 Challenges and Risks of Vaccination 5.1 Vaccine failure and antigen drift There are various reasons why poultry still fall ill after vaccination. For instance, the high concentration of maternal antibodies in poultry can inhibit the immune response triggered by vaccines, resulting in poultry being prone to infection even after vaccination (Pan et al., 2022; Li et al., 2024). In addition, improper vaccine management, such as the use of expired vaccines, poor storage conditions, or failure to administer vaccines at the prescribed time, can significantly reduce the efficacy of vaccines and thereby trigger disease epidemics (Cargill, 1999; Ma et al., 2021). Antigenic drift refers to the gradual accumulation of mutations in viral surface proteins, which poses a significant challenge to prevention and control efforts. Viruses such as avian influenza and infectious bronchitis can thereby evade the immune protection provided by existing vaccines. Once antigenic variation occurs, the protective effect of the vaccine will be partially or even completely lost. Therefore, continuous monitoring and regular updates of the vaccine strain are necessary to protect poultry all the time (Swayne et al., 2015; Jordan, 2017). 5.2 Biosecurity issues: risks of rising virulence and environmental spread of live vaccines Although live attenuated vaccines have a good prevention and control effect, there is a risk of virulence recovery, that is, the vaccine strain becomes pathogenic again, and then causes diseases in vaccinated or susceptible poultry

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 6 flocks. If biosecurity measures are inadequate or vaccine strains are prone to spread and mutate, this risk will be higher and even new pathogens with stronger toxicity may emerge. The spread of live vaccine strains in the environment is also a biosafety hazard, as these strains may spread to unvaccinated poultry and even wild birds, making disease prevention and control efforts more complicated. Strictly implementing vaccine handling norms, monitoring accidental transmission situations, and using inactivated vaccines or recombinant vaccines when necessary can reduce these risks (Badakaya et al., 2021). 5.3 Immunosuppression and mixed infections affecting vaccine efficacy Immunosuppression in poultry, whether due to stress, malnutrition, or concurrent infection with other diseases, will severely weaken the immune response triggered by vaccines, resulting in poorer protective effects and making poultry more prone to illness (Badakaya et al., 2021). If poultry are simultaneously infected with other pathogens, such as infectious bursal disease virus, mycoplasma, etc., it will further weaken the immunity brought by vaccines and make the condition more severe (Bhuiyan et al., 2021). The presence of immunosuppression or mixed infections in poultry highlights the importance of comprehensive management of poultry flock health, including ensuring good nutritional supply, implementing biosecurity measures, and regularly monitoring diseases. Only in this way can vaccines achieve the best effect and reduce the risk of vaccination failure (Badakaya et al., 2021; Bhuiyan et al., 2021). 6 Emerging Technologies and Future Development Directions 6.1 Promising technologies New achievements in the field of poultry vaccines include the development of RNA vaccines and the application of nanocarriers, which can precisely deliver antigens and enhance the immune effect. Nanotechnology means, such as virus-like particles (vlp), can simulate viral structures without genetic material, providing a safer and more immune-effective alternative to traditional vaccines (Raji et al., 2024). These innovations can make vaccines more stable, achieve precise delivery, and reduce the occurrence rate of adverse reactions. They are powerful tools for the future prevention and control of poultry diseases (Abdelaziz et al., 2024; Bodman-Harris et al., 2024). People are still exploring new vaccination systems, including follicular administration and new adjuvant formulations, to enhance vaccine absorption efficiency and immune response. Combining introvulation inoculation and large-scale inoculation methods with advanced vector platforms can efficiently carry out large-scale immunization and even holds the promise of preventing multiple pathogens with a single injection (Francis, 2021; Bodman-Harris et al., 2024). These technologies are expected to play a significant role in the prevention and control of existing and emerging infectious diseases in poultry (Abdelaziz et al., 2024). 6.2 Precision immunization and data-driven strategies Precision immunization optimizes vaccination plans through data-driven approaches, monitors herd immunity, strengthens disease prevention and control, and reduces vaccine waste. The use of digital tools for vaccine traceability enables real-time tracking of vaccine usage, batch information, and the health status of poultry flocks, which helps to respond quickly to the epidemic and enhance the effectiveness of the overall vaccination program (Abdelaziz et al., 2024). Personalized immunization plans tailored to different poultry flocks based on genetic, health and environmental data are becoming the development trend of poultry health management. These strategies can help determine the most applicable vaccine type, dose and vaccination time for each poultry flock, improve the protective effect, and reduce the risk of vaccine failure caused by factors such as maternal antibody interference and local pathogen variation (Ravikumar et al., 2022; Abdelaziz et al., 2024). 6.3 Enhance the efficacy of vaccines by integrating nutrition and genetic breeding Combining vaccination with nutritional intervention and genetic breeding is an overall strategy to ensure the health of poultry and enhance their disease resistance. Adjusting the feed formula and adding immune enhancers or probiotics can enhance the immune response triggered by vaccines and improve the overall resistance of the

Journal of Vaccine Research, 2025, Vol.15, No.1, 1-9 http://medscipublisher.com/index.php/jvr 7 poultry flock (Abdelaziz et al., 2024). In particular, the intestinal microbiota of poultry has a significant impact on vaccine efficacy and disease development (Astill et al., 2022). Through genetic selection and breeding of disease-resistant poultry breeds, combined with advanced vaccination strategies, the occurrence rate and severity of infectious diseases in poultry flocks can be further reduced. Promoting breeding programs with biotechnology and combining them with innovative vaccines provides a synergistic development path for achieving sustainable poultry farming, improving animal welfare, and reducing the use of antibiotics (Abdelaziz et al., 2024). 7 Concluding Remarks Vaccination has always been a key measure in preventing poultry diseases and enhancing the efficiency of poultry farming, and there are various strategies applicable to different poultry breeds, farming types and disease risks. Traditional inactivated vaccines, live vaccines, as well as new recombinant vaccines and vector vaccines have all been widely used, but their actual efficacy is affected by the vaccination method, vaccination time, and the degree of matching between the vaccine and the epidemic strain. Practice has shown that large-scale operation methods such as vaccination in hatcheries are more effective, enabling a large number of poultry to obtain higher and more balanced immune protection. However, getting vaccinated on the spot in the breeding farm is more labor-intensive and the immune effect is also likely to be uneven. Although there is a wide variety of vaccines, it is still difficult to achieve an ideal vaccination coverage rate, especially under different breeding models and for poultry species such as ducks and pearl chickens that have fewer vaccines in hatcheries. In order to effectively control diseases, it is very necessary to update vaccines in a timely manner to deal with antigen variations, unify the data on vaccine efficacy evaluation, and combine vaccination with disease surveillance and biosecurity measures. When conducting preventive vaccinations, special attention should be paid to poultry breeds that are prone to infection and areas with high disease incidence. The vaccination strategy should be combined with the local disease epidemic situation and the actual breeding situation. In areas with high disease threats and frequent outbreaks, implementing emergency vaccination programs, such as circular vaccination around the areas where the epidemic has occurred, can achieve good results. However, at the same time, it needs to be combined with rapid diagnosis and control measures. Cost-benefit analysis shows that the most effective strategy is to widely cover all kinds of poultry breeds and breeding types. Among them, vaccination in hatcheries has the highest cost performance in the comprehensive breeding system. For regions with scarce resources or where some vaccines are difficult to obtain, focusing on vaccinating breeding chickens, laying hens and broilers can also achieve herd immunity and reduce the risk of epidemic outbreaks. Only by continuously monitoring the efficacy of vaccines and the mutation of the virus can strategies be adjusted in a timely manner to maintain the protective effect. To enhance the effectiveness of poultry vaccination, it requires the collaborative efforts of veterinarians, farmers, researchers and policymakers. Interdisciplinary collaboration is crucial for the development of a new generation of vaccines, the improvement of vaccination techniques, and the integration of vaccination with nutrition supply, genetic breeding, and aquaculture management. At the policy level, the approval process for vaccines should be simplified, investment in the research and development of new vaccine technologies should be increased, and a complete monitoring and traceability system should be established to track the efficacy of vaccines and the development trend of diseases. Only by promoting cooperation among all parties and formulating scientific policies can the poultry farming industry better resist emerging disease threats, safeguard animal welfare and achieve sustainable development. Acknowledgments The author extends his sincere thanks to two anonymous peer reviewers for their feedback on the initial draft of this study. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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Journal of Vaccine Research, 2025, Vol.15, No.1, 10-22 http://medscipublisher.com/index.php/jvr 10 Research Insight Open Access Factors Influencing Long-Term Vaccine-Induced Immunity JieZhang Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China Corresponding email: jie.zhang@jicat.org Journal of Vaccine Research, 2025, Vol.15, No.1 doi: 10.5376/jvr.2025.15.0002 Received: 17 Nov., 2024 Accepted: 02 Jan., 2025 Published: 15 Jan., 2025 Copyright © 2025 Zhang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Zhang J., 2025, Factors influencing long-term vaccine-induced immunity, Journal of Vaccine Research, 15(1): 10-22 (doi: 10.5376/jvr.2025.15.0002) Abstract This study explores the key principles that can sustain immune effects for a long time, such as the production of memory B cells and T cells, the process by which antibodies become more "powerful", and plasma cells that can function for a long time. The article also explains how different types of vaccines, added auxiliary components, vaccination methods and timing affect the body's memory of the immune response. It also analyzes personal-related factors such as age, genetic characteristics and whether there are other diseases. This study also explored the impact of nutritional status, lifestyle and the microorganisms in the intestinal tract on the regulation of the immune system. This review offers solutions to the problem of weakened immunity, with a focus on methods such as booster immunization and mixed vaccination, which are particularly helpful for people with poor immunity. This study also suggests adopting a precise vaccine development approach, combined with population data analysis, to provide guidance for the development of a new generation of vaccines with better protective effects and longer durations. Keywords Vaccine-induced immunity; Memory B and T cells; Immunosenescence; Adjuvants; Booster strategies 1 Introduction The long-term immune protection provided by vaccines is crucial for preventing infectious diseases, reducing the harm of diseases and preventing large-scale outbreaks of epidemics. Vaccines can generate long-lasting immune memory by forming long-existing memory T cells and B cells and continuously generating antibodies, which makes vaccines highly effective in controlling diseases such as tuberculosis, hepatitis B, Ebola virus and COVID-19 (Hennig et al., 2008; Han et al., 2021; Alexandre et al., 2023; Moore et al., 2023; Berber and Rose, 2024). However, due to the interaction of multiple factors such as the human body's own condition, living environment, and the vaccine itself, there are significant differences among different individuals and even different groups in terms of how long and how strong the immune effect produced by the vaccine can last (Fischinger et al., 2018; Zimmermann and Curtis, 2019; Lynn et al., 2021). The core issue of the research is why the immunity generated by vaccines weakens over time and to identify the factors that determine how long immune memory can last. The challenges faced by this study include understanding the impact of genetic differences, age, gender, other diseases and environmental factors on immune responses (Hennig et al., 2008; Fischinger et al., 2018; Zimmermann and Curtis, 2019; Fonzo et al., 2023). In addition, it is necessary to study how to adjust the gut microbiota, improve vaccine types, and optimize booster vaccination strategies to enhance the long-term protective effect of vaccines (Zimmerman and Curtis, 2019; Lynn et al., 2021). The continuous mutation of the virus, coupled with the fact that the elderly and those with weaker immune systems need longer-term immune protection, makes the research work even more difficult (Goronzy et al., 2020; Berber and Ross, 2024). This study will explore various known factors that affect the long-term immune effect of vaccines. It will analyze the immunological principles of the formation of persistent immune memory, including the generation and maintenance of memory B cells and T cells, as well as the process of increasing antibody affinity. This study will also explore factors related to the human body itself, the external environment and vaccines, which can affect the duration and effectiveness of the vaccine's protective effect. Finally, the current difficulties faced by the research will be pointed out, and the future directions for optimizing vaccine strategies will be looked forward to, striving to ensure that different groups of people can obtain strong and long-lasting immune protection.

Journal of Vaccine Research, 2025, Vol.15, No.1, 10-22 http://medscipublisher.com/index.php/jvr 11 2 The Immunological Basis of Long-Term Vaccine-Induced Immunity 2.1 The formation mechanism of memory B cells and long-lived plasma cells The emergence of memory B cells and long-lived plasma cells is the key to maintaining long-term antibody immunity in the human body. When the human body comes into contact with an antigen, B cells will be activated and then undergo changes through germinal center reactions. During this process, B cells will continuously divide and increase in number, and somatic mutations will also occur. Eventually, cells that can better bind to the antigen will be selected. This series of processes generates two important types of cells: memory B cells, which act like a "reserve force" and can respond quickly when encountering the same antigen next time. There are also plasma cells capable of secreting antibodies (Cancer and Tomayko, 2021; Ripperger and Bhattacharya, 2021; Roy et al., 2023). Long-lived plasma cells will run to "sanctuaries" such as bone marrow, where they can survive for several years or even decades, and can continuously produce antibodies without the need for constant antigen stimulation (Slifka and Ahmed, 1998; Akkaya et al., 2019; Ionescu and Urschel, 2019). Memory B cells are not exactly the same. They differ in antibody types, mutation conditions, and distribution locations, and are distributed in the spleen, blood, and body barrier tissues. These cells do not divide normally, have a long survival time and are in a "dormant" state. They will not be awakened until they encounter antigens again. Once activated, they can quickly transform into plasma cells capable of secreting antibodies (Ochsenbein et al., 2000). Scientists are still conducting continuous research on how memory B cells persist and renew over the long term, as well as their relationship with plasma cells (Cancro and Tomayko, 2021; Inoue and Kurosaki, 2023). 2.2 The role of memory T cells in continuous immune protection Although the previous discussion mainly focused on the immunity brought by B cells, T cells, especially memory T cells, are also crucial for vaccines to provide long-term protection. During the germinal center reaction process, memory T cells assist B cells to help form and maintain memory B cells and plasma cells that can better bind to antigens. This auxiliary effect is crucial for memory B cells to smoothly transform into plasma cells after re-exposure to antigens. Only in this way can the human body rapidly and forcefully initiate the second immune response (Ochsenbein et al., 2000; Roy et al., 2023). In addition, memory T cells can also expand the coverage of the immune response and enhance the immune effect, especially when dealing with mutated bacteria. These cells can remain in a "standby" state for a long time. Once the body is reinfected, they will immediately take action. It is precisely because of this ability of memory T cells that many vaccines can exert protective effects for a long time, which also makes up for the deficiency of memory B cells in producing antibodies for defense (Ochsenbein et al., 2000; Roy et al., 2023). 2.3 Affinity maturation and the production of long-term antibodies Affinity maturation is a process that occurs in the germinal center. During this process, the receptors used by B cells to recognize antigens will become more likely to bind to antigens through mutations and screening of the cells themselves. After such changes, the newly generated memory B cells and plasma cells can produce antibodies that bind more closely to antigens. This step is very crucial and plays a decisive role in achieving effective and long-lasting immune protection (Inoue, 2023; Roy et al., 2023). The ultimate effect of affinity maturation directly affects whether the antibody response produced by the body after vaccination is good or not, and how long this response can last. The long-term presence of antibodies is due to the functioning of long-lived plasma cells in the bone marrow. These cells can continuously secrete antibodies without further contact with antigens. They have always been there, ensuring the content of protective antibodies in the body, just like the "first line of defense" against reinfection. The compatibility between mature memory B cells and long-lived plasma cells is fundamental to maintaining the long-term immunity brought by vaccines (Slifka and Ahmed, 1998; Ionescu and Urschel, 2019; Akkaya et al., 2019; Roy et al., 2023).

Journal of Vaccine Research, 2025, Vol.15, No.1, 10-22 http://medscipublisher.com/index.php/jvr 12 3 Vaccine-Related Factors 3.1 The impact of vaccine types on the duration of immunity Different types of vaccines have a significant impact on how long the immune response can last and how effective it is. Just like mRNA vaccines and protein vaccines with added auxiliary components, it has been proven that they can enable the human body to produce strong and long-lasting antibodies and also generate memory B cells. Moreover, vaccines with auxiliary components generally have better immune effects in terms of intensity and duration than those without auxiliary components. If inactivated vaccines are used in combination with powerful auxiliary components like AS03, the response range of memory B cells can be expanded and the duration prolonged. Attenuated live vaccines have long been renowned for their ability to simulate the natural infection process and provide people with long-lasting immunity (Ellebedy et al., 2020; Grigoryan et al., 2024). The selection of different types of vaccines will also affect the function of different B cells. For example, compared with vaccines without auxiliary components, inactivated vaccines with auxiliary components can not only activate the original immune memory of the human body, but also activate immature B cells that have not been exposed to antigens. In this way, the immune response is more comprehensive and lasts longer (Ellebedy et al., 2020). These differences indicate that choosing the right type of vaccine is crucial for achieving long-term immune protection. 3.2 The role of adjuvants in enhancing memory responses The auxiliary components added to vaccines play a crucial role in determining how strong the immune memory brought by the vaccine is, how effective it is, and how long it can last. Studies comparing the auxiliary components such as AS01, AS03, AS04 and alum have found that the auxiliary system containing specific components generally enables the human body to produce higher levels of antibodies, and the antibodies and antigens bind more firmly than vaccines using only alum. It can also prolong the response of memory B cells for a longer time (Budroni et al., 2021). In particular, AS03 has been proven to enhance the intensity of memory B-cell responses, prolong such responses, and increase the types of cells involved in the responses. Over time, it helps B-cells that can widely neutralize viruses develop and mature (Grigoryan et al., 2024; Lian et al., 2024). The auxiliary components in vaccines can enhance immune memory, which is related to activating the body's innate immune capacity. This activation process is crucial. It can help T follicular helper cells change and also transform B cells into plasma cells that can function for a long time. If the dosage of auxiliary components is increased, these effects can be made stronger, enabling people to achieve better and more lasting immune memory (Pal and Iyer, 2025). 3.3 The influence of administration routes and regimens on immune persistence The method and timing of vaccination are key factors in determining how long immune protection can last. Getting a booster shot, especially when the intervals are appropriate, can cause the body to produce more antibodies, and the response of memory B cells is also stronger and lasts longer, just like what is seen when children are vaccinated with influenza vaccines with added auxiliary components (Kazmin et al., 2023). The duration of the interval between each vaccination can affect the growth and maturation of memory B cells. Shorter intervals lead to a faster increase in the number of cells. A longer interval helps cells become more "powerful", allowing immune memory to last longer (Ellebedy et al., 2020; Kazmin et al., 2023). The effect of immune response varies depending on the way vaccines are administered. Take the intramuscular injection of vaccines with auxiliary components as an example. This method can enable the human body to produce strong and long-lasting antibody immunity and cellular immunity. However, at present, scientists are still exploring other vaccination methods with the aim of enhancing immune memory and improving the protective effect of the vaccine (Kazmin et al., 2023; Li et al., 2024). Therefore, when vaccinating everyone, carefully determining the dosage of the vaccine, properly arranging the intervals between two vaccinations, and choosing the appropriate vaccination method are all crucial for the long-term protective effect of the vaccine on the human body.

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