Journal of Vaccine Research 2024, Vol.14 http://medscipublisher.com/index.php/jvr © 2024 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Publisher
Journal of Vaccine Research 2024, Vol.14 http://medscipublisher.com/index.php/jvr © 2024 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), 2024, Vol. 14, No. 6 ISSN 1927-6486 http://medscipublisher.com/index.php/jvr © 2024 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 Long-Term Immunity Post Hepatitis B Vaccination: A Systematic Review WeiminSun Journal of Vaccine Research, 2024, Vol. 14, No. 6, 278-286 Efficacy of Combined Measles, Mumps, and Rubella Vaccines Jianbang Chen Journal of Vaccine Research, 2024, Vol. 14, No. 6, 287-296 The Role of T-cell Responses in Universal Influenza Vaccine Efficacy Jianhui Li Journal of Vaccine Research, 2024, Vol. 14, No. 6, 297-306 Comparative Analysis of Bivalent, Quadrivalent, and Nonavalent HPV Vaccines Caijuan Shou, Xiaoping Cai Journal of Vaccine Research, 2024, Vol. 14, No. 6, 307-315 mRNA Technology in Vaccine Development: Current Status and Future Prospects Xingzhu Feng Journal of Vaccine Research, 2024, Vol. 14, No. 6, 316-323
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 278 Systematic Review Open Access Long-Term Immunity Post Hepatitis B Vaccination: A Systematic Review WeiminSun Sinovac (Dalian) Vaccine Technology Co., Ltd., Dalian, 116620, Liaoning, China Corresponding author email: weimin@sinovac.com Journal of Vaccine Research, 2024, Vol.14, No.6 doi: 10.5376/jvr.2024.14.0026 Received: 10 Sep., 2024 Accepted: 25 Oct, 2024 Published: 10 Nov., 2024 Copyright © 2024 Sun, 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: Sun W.M., 2024, Long-term immunity post hepatitis b vaccination: A systematic review, Journal of Vaccine Research, 14(6): 278-286 (doi: 10.5376/jvr.2024.14.0026) Abstract This study talks about how long the hepatitis B vaccine can protect people. It explains how the immune system keeps working after vaccination and why this is important for fighting HBV around the world. The results show that the vaccine makes the body produce antibodies and immune cells, giving strong and lasting protection. Over time, the amount of antibodies may go down, but most healthy people can still fight off the virus because their immune system remembers it. However, not everyone is the same. People with weaker immune systems and people living in places with less vaccine coverage may not stay protected as well. The study also looks at whether people need booster shots and how well the current vaccines work against new virus strains. It checks how different things, like vaccination schedules, age, and health problems, change how well the vaccine works. Because of global vaccination programs, there are now fewer HBV infections and liver disease cases. The study says we should keep making vaccination plans better, do more health checks, and create new vaccines to help get rid of HBV for good. Keywords Hepatitis B vaccine; Long-term immunity; Immune memory; Booster dose; Vaccine escape 1 Introduction Hepatitis B virus (HBV) is a serious health problem all over the world. It causes both short-term and long-term liver problems. Many people get sick or die because of it. Chronic HBV infection is even worse. It can cause liver scars (cirrhosis) and liver cancer (HCC), leading to more than 800 000 deaths every year (Flores et al., 2022). HBV is one of the main causes of long-term liver disease. In 2022, about 296 million people around the world were living with it. This puts a big strain on healthcare systems and the economy (Flores et al., 2022). The highest rates are in places like Sub-Saharan Africa, Southeast Asia, and the Western Pacific. In these areas, more than 8% of people have HBV. Most infections happen when the virus passes from mothers to babies or spreads among young children, causing health problems that last a lifetime. Even with the progress made, there were still about 6.3 million kids under five living with HBV in 2019 (Wang et al., 2023). This shows that more work is still needed. The HBV vaccine has helped a lot around the world. It has lowered infection rates in kids and teens. But not all places have good vaccine coverage. For example, only 42% of babies globally get the first dose at birth, which is very important to stop the virus from passing from mother to child (Flores et al., 2022). Poor countries have an even harder time because healthcare services are not as good, and vaccines can be expensive (Chen et al., 2015). Making the HBV vaccine was a big success for public health. Since the 1980s, the recombinant HBV vaccines have been very safe and over 95% effective at preventing chronic infection (Gomes et al., 2019). Now, 190 countries vaccinate babies. This has caused a big drop in HBV cases among children. In Taiwan, where the vaccine was used early, chronic HBV in kids dropped by 90%, and childhood liver cancer cases fell a lot within 20 years (Kao, 2015). Still, there are challenges. Vaccine protection can weaken over time, especially for people who got their shots as babies. Experts are still studying if adults need booster shots to stay safe. Also, new types of HBV that the vaccine might not fully cover, and gaps in vaccine access between countries, show we must keep watching and researching.
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 279 This study will focus on how long HBV vaccine protection lasts. It will look at different groups and ages to see how strong the immunity is. It will also check how the immune system works after vaccination and what can make protection weaker. The study hopes to help health workers and leaders make better vaccine plans and help reach the WHO goal to get rid of HBV by 2030. 2 Mechanism of Immunity Post HBV Vaccination After getting the hepatitis B vaccine, the body uses both antibodies and immune cells to fight the virus. These two work together to keep protection strong for a long time. 2.1 Humoral immune response The main job of the HBV vaccine is to help the body make antibodies against the hepatitis B surface antigen (anti-HBs). If a person's anti-HBs level reaches 10 mIU/mL or higher, it means they are protected and the vaccine did its job (Marshall et al., 2010). Antibody levels go up after the vaccine shots, but they slowly drop over time. Some people lose them faster than others (Chlibek et al., 2011). Even when the levels get low, the immune system can still react quickly if it sees the virus again or if a booster shot is given (Klinger et al., 2018). Long-term studies show that most healthy people stay protected for many years, even if their antibody levels become too low to measure (Gilca et al., 2013). 2.2 Cellular immunity T cells, a kind of immune cell, are also really important after getting the HBV vaccine. Even when no antibodies are found, the body still keeps memory B cells and T cells ready to fight HBV (Simons et al., 2016). Studies show that these T cells can stay active for decades and recognize parts of the virus when needed (Wu et al., 2011). That's why people who got vaccinated almost never get sick with HBV, even if their antibody levels fall (Madaliński et al., 2015). 2.3 Interaction between immune memory and exposure Sometimes, people naturally come into contact with HBV without getting sick. This helps keep their immune system alert. It happens a lot in places where HBV is common (Chaves et al., 2012). When this happens, memory B cells and T cells quickly react, and antibody levels can rise again for a short time (Wu et al., 2011). Booster shots can also wake up the immune system, even years after the first vaccination (Lu et al., 2008). This shows that immune memory is very important for staying protected for the long haul. In short, antibodies and immune cells, with the help of memory cells, work together to keep people safe after the HBV vaccine. Scientists are still working on better vaccine plans and trying to understand immune memory more deeply to help stop HBV around the world (Ma et al., 2019; Ciotti et al., 2020). 3 Duration of Immunity It's really important to know how long the hepatitis B vaccine can protect people. It helps us see how well the vaccine works to stop HBV and related diseases over time. Many things can change how long protection lasts, like when you get the shots, how your body reacts, and the vaccine schedule. 3.1 Longevity of protection in general populations Studies show that the HBV vaccine gives strong, long-lasting protection. It can stop infections and chronic HBV for many years. One review said over 95% of healthy people stayed protected for at least 30 years after finishing all their shots (Wu et al., 2011). In Taiwan, where they started giving the vaccine to kids early, the number of children with chronic HBV dropped from 10% to less than 1% over 30 years (Chen et al., 2015). In places where HBV is common, small exposures to the virus help keep people's immune systems active. For example, a 23-year study showed that 48% of people who got the vaccine as kids still had antibodies. Even better, 75% to 100% showed a strong immune response after getting a booster, proving that their immune memory was still working (Wu et al., 2011).
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 280 3.2 Decline in antibody levels over time Antibody levels (anti-HBs) usually go down over time. Most people start losing some protection 5 to 10 years after getting vaccinated. In Canada, one study found that 82% of kids vaccinated at ages 8~10 had good antibody levels after five years, but only 68% still did after 15 years (Gilca et al., 2013). Figure 1 shows how antibody levels drop over 15 years. Even though they fall, most people still had some antibodies left. After getting a booster, their antibody levels quickly went back up. Figure 1 Anti-HBs titers distribution at different study time points (Adpoted from Gilca et al., 2013) Even when antibody levels fall below 10 mIU/mL (the level seen as "protected"), most people stay safe because their immune system remembers HBV (Wu et al., 2018; Ahonen et al., 2022). For example, in Israel, out of more than 20 000 people vaccinated as babies, only 0.004% got HBV even though 66% had no detectable antibodies after 15 years (Klinger et al., 2018). This shows just how important immune memory is. 3.3 Comparison between pediatric and adult vaccinees How long protection lasts also depends on when you got your shots. Kids who got vaccinated at birth often lose their antibodies faster than adults. That's probably because babies' immune systems aren't fully developed, so their first response is weaker (Lu et al., 2008). One study found that 63% of teenagers who were vaccinated as newborns had no detectable antibodies 15~18 years later. But after a booster shot, 89% of them had a strong immune response, meaning their immune memory was still working (Lu et al., 2008). Adults who get vaccinated later in life tend to keep their antibodies longer. A study from Beijing showed that 86% of adults still had good antibody levels one year after vaccination, and 54% still did after ten years. Overall, adults had higher antibody levels compared to kids (Shen et al., 2022). Because of these differences, it's important to keep checking on kids who got vaccinated early, especially as they grow up. Some kids, especially in high-risk groups, might need booster shots. But for low-risk groups, extra shots might not be needed. 4 Factors Influencing Long-Term Immunity Many things can change how long the hepatitis B vaccine keeps you safe. The dose you get, when you get the shots, how your body reacts, and if you have a weak immune system — all these matter. These things decide how strong your protection is and if you might need booster shots later.
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 281 4.1 Vaccine dosage and schedule The amount of vaccine and the timing of the shots are really important. The usual three-shot plan (at 0, 1, and 6 months) works well for most healthy kids and adults. Over 90% of them become protected (Marshall et al., 2010). But sometimes, people follow different plans: 1) Fast Schedules: Travelers and people who need quick protection get shots at 0, 7, and 21 days, plus a booster at 12 months. This gives fast protection, but the antibody levels drop faster than with the regular plan (Launay et al., 2016). For example, healthcare workers who used the fast schedule needed extra booster shots after 5~7 years. Figure 2 shows that different people might need different vaccine plans. Figure 2 Recommended hepatitis B virus vaccination schemes (Adpoted from Di Lello et al., 2022) Image caption: The hepatitis B immunization schedule is flexible, but minimal intervals and ages need to be observed. The recommended dose varies (5~40 μg of hepatitis B surface antigen protein/mL) depending on the individuals’ age and the vaccine brand. aMonovalent hepatitis B vaccine 0.5 mL must be used for the at birth immunization (HepB-BD). Immunocompromised adults or patients under dialysis require larger or additional doses of the hepatitis B vaccine; bCombined hepatitis B, diphtheria, tetanus, adsorbed acellular pertussis, inactivated poliovirus vaccine. This vaccine cannot be administered at birth, before 6 postnatal weeks, or at age ≥ 7 years; cHeplisav-B is a vaccine recently approved for adults; it has a novel adjuvant and its recommended schedule is two doses 1 mo apart. HepB3: Three doses of hepatitis B vaccine; HepB-BD: Monovalent single dose of the hepatitis B virus vaccine; HBIG: Hepatitis B Immunoglobulin (Adpoted from Di Lello et al., 2022) 2) Low-Dose Vaccines: Pediatric doses are effective in generating initial immunity but may result in lower long-term antibody persistence. In one study, children vaccinated at birth showed a 40~60% decline in protective anti-HBs levels by adolescence (Gilca et al., 2013). 3) Booster Shots: Some groups, like healthcare workers or people living where HBV is common, often need booster shots later. A study in Taiwan showed that giving a booster 10~15 years after the first shots helped more than 90% of people get back their protection (Wu et al., 2011). 4.2 Individual variability in response Not everyone's body reacts the same after getting the vaccine. Some people naturally build stronger protection than others. 1) Genes: About 5~10% of people don't respond well because of their genes. These "non-responders" don't make enough antibodies after their shots (Simons et al., 2016). 2) Age at Vaccination: Babies who get vaccinated at birth lose their antibodies faster than kids or adults who get vaccinated later. One study found that by age 15, about 50% of kids vaccinated as newborns lost their antibodies, compared to 30% of kids vaccinated at 5 years old (Lu et al., 2008). 3) Health and Habits: Things like diabetes, smoking, or being overweight can make the vaccine work less well. For example, people with diabetes had 20~30% lower protection rates than healthy people in several studies (Buti et al., 1992).
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 282 4.3 Immunocompromised and special populations Some people need different vaccine plans because their immune systems are weaker: 1)People with HIV: Only 40~60% of people with HIV reach good protection levels after regular shots. Giving them double doses helps more, raising protection to around 80% (Chaiwarith et al., 2019). 2)Dialysis Patients: Hemodialysis patients often fail to achieve long-lasting immunity, with over 50% losing detectable anti-HBs levels within 1~2 years. Frequent boosters and high-dose regimens are necessary to maintain protection (Tsouchnikas et al., 2007). 3)Pregnant Women and Newborns: Babies born to mothers with HBV are at high risk. Giving newborns a birth-dose vaccine plus hepatitis B immunoglobulin (HBIG) right after birth can protect over 95% of them, even in places where HBV is common (Liu et al., 2019). The vaccine dose, timing, and your health all affect how long protection lasts. Adjusting vaccine plans, giving boosters, or using higher doses when needed can help keep more people safe. Scientists are still working to make vaccines even better and protect more people around the world. 5 Long-Term Outcomes of HBV Vaccination Programs Hepatitis B vaccination programs have made a big difference around the world. They have cut down HBV infections, slowed the spread of the virus, lowered serious liver diseases, and saved a lot of healthcare money. As more people get vaccinated, these good results will likely get even better. One day, we might even wipe out HBV as a major health problem. 5.1 Reduction in HBV prevalence and transmission Vaccination programs have caused big drops in HBV cases and virus spread, especially in places where HBV used to be very common. For example, Taiwan started giving HBV shots to all newborns in 1984. Ten years later, HBV infections in kids under five dropped from 10% to less than 1% (Chen et al., 2015). China saw the same trend. Before vaccination, 9.7% of young kids had HBV in 1992. After adding the vaccine to national programs, the rate fell to 0.3% by 2014 (Liu et al., 2019). In Africa, there are still some problems, but in cities where more kids get vaccinated, HBV rates have gone down a lot too (Wang et al., 2023). Besides lowering infection rates, vaccines also stop moms from passing HBV to their babies. Giving newborns a shot at birth plus hepatitis B immunoglobulin (HBIG) works really well. In Taiwan, mother-to-baby HBV transmission dropped from 16.9% to less than 2% after the program started (Kao, 2015). 5.2 Prevention of chronic HBV and liver diseases The HBV vaccine doesn't just stop infections. It also lowers serious liver problems like cirrhosis and liver cancer (HCC) (Lee et al., 2020). In Taiwan, after they started giving the vaccine to all babies, liver cancer cases in kids fell by 67% over 20 years (Kao, 2015). In Alaska, indigenous groups used to have a lot of HBV cases. After vaccination programs began, liver diseases in these groups dropped a lot too (Flores et al., 2022). In sub-Saharan Africa, where liver cancer is very common because of HBV, vaccines for babies also showed strong protection. A study in Gambia found almost no liver cancer in vaccinated kids (Gilca et al., 2013). Also, with fewer chronic HBV infections, fewer people end up with cirrhosis. This helps save hospital costs and reduces the suffering caused by late-stage liver disease. 5.3 Cost-effectiveness of universal vaccination HBV vaccination doesn't just help health. It also saves a lot of money. Studies show vaccination programs are very cost-effective, especially where HBV is common. In China, every dollar spent on the HBV vaccine saved about $14 in future medical bills (Wang et al., 2019; Liu et al., 2020).
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 283 In Taiwan, their vaccination program prevented about 4 200 liver cancer cases and saved around $1 billion in healthcare costs over 25 years (Chen et al., 2015). Worldwide, by cutting down the need for liver transplants and expensive medicines, vaccination programs have helped make healthcare systems stronger and less costly. Low- and middle-income countries, which often have more HBV cases, also benefit a lot. Thanks to support from groups like GAVI (the Global Alliance for Vaccines and Immunization), many countries have been able to start HBV vaccination programs. For example, with GAVI's help, vaccination rates in Africa rose to over 80%, leading to big health wins and big savings (Liu et al., 2019). 6 Challenges and Knowledge Gaps Hepatitis B vaccination programs have done a lot of good. But there are still some problems and questions. We still need to find out if booster shots are really needed, if the protection lasts for a very long time, and if vaccines work well against new types of HBV. 6.1 Booster dose necessity There is still no clear answer about booster shots. Most studies say that healthy people who finish their first set of shots stay protected for life, even when their antibody levels go down (Madaliński et al., 2015). But some research shows that people who often get exposed to HBV, like healthcare workers, might need booster shots now and then to stay safe (Lu et al., 2008). Right now, WHO says healthy people don't need booster shots. But experts are still talking about whether special groups should get extra doses (Chlibek et al., 2011). 6.2 Gaps in longitudinal data Another big problem is that we don't have enough long-term studies. We know protection usually lasts 20~30 years after getting the shots, but we are not sure what happens after that (Gilca et al., 2013). Many studies don't follow kids who were vaccinated as babies all the way into adulthood, especially in poorer countries. This makes it hard to know exactly how long the vaccine keeps working. In places where HBV is common, people may naturally get exposed to the virus again. This can boost their immune system without them knowing. That makes it even harder to figure out how much of their protection comes just from the vaccine (Simons et al., 2016). Setting up programs to follow people for many years and collect good data would help solve this problem. 6.3 Emerging variants and vaccine effectiveness HBV is a virus that can change over time. Some new types, called "vaccine-escape variants," have already been found. These new types show up more often in places where lots of people have been vaccinated (Kao, 2015). This has made some experts worry that the vaccines we use today might not work as well in the future. For now, the vaccines we have still work very well. But if more new virus types show up, we might need to make new vaccines or find other ways to stay protected (Flores et al., 2022). That's why it's really important to keep checking HBV strains around the world. We need to catch any changes early before they become a big problem. 7 Future Directions 7.1 Development of next-generation vaccines Scientists are working on new vaccines to fix the problems with the ones we have now, especially to deal with new types of HBV. The new vaccines might target more parts of the virus, like the core antigen. This could help stop virus types that the current vaccines can't fully cover (Flores et al., 2022). They are also trying new adjuvants —special ingredients that help vaccines work better. These could help people like older adults and those with weak immune systems get stronger protection (Kao, 2015). Some new vaccines are being made with DNA or mRNA technology. These might last longer and cut down the need for booster shots (Simons et al., 2016). 7.2 Improved monitoring and surveillance systems We need better systems to track how well HBV vaccination programs are working over time. Stronger national and global databases could help us see how long antibodies last, how good immune memory is, and how often people still get infected after vaccination (Razavi-Shearer et al., 2018). If we also track different types of HBV, we can spot new virus types early and update vaccines when needed (Launay et al., 2016). It's also important to keep
Journal of Vaccine Research 2024, Vol.14, No.6, 278-286 http://medscipublisher.com/index.php/jvr 284 track of who might need booster shots, especially people at higher risk. This would make vaccination programs even better. 7.3 Personalized vaccination approaches Different people react differently to vaccines. That's why we may need to make vaccination plans more personal. Changing the timing or dose of vaccines for certain groups—like people who don't respond well or people with higher risk of infection—could give stronger and longer protection (Gilca et al., 2013). For people with weak immune systems, higher doses, better adjuvants, and more frequent boosters might be needed to keep them safe (Klinger et al., 2018). In the future, tools like genetic testing might help doctors find the best vaccination plan for each person. This could help vaccines work even better and save money too. 8 Concluding Remarks Hepatitis B vaccines do a good job of protecting people. They help the body fight the virus by making both antibodies and immune cells. Even when antibody levels get so low that tests can't find them, the body's memory still knows how to fight HBV and can protect people for many years. But protection doesn't last the same for everyone. People with weak immune systems, or people living in places where not many get vaccinated, might lose protection faster. Vaccines have already helped a lot by lowering HBV infections, stopping the virus from spreading, and cutting down liver disease. Still, some questions remain. We are still trying to figure out if booster shots are needed and if new types of HBV might cause problems for current vaccines. The big drop in HBV cases shows how important it is to keep vaccination programs strong and to reach even more people. Giving the vaccine to everyone, especially in places where HBV is common, is key to meeting the World Health Organization's goals. Vaccination programs also save a lot of money, even in countries that don't have much money (Razavi-Shearer et al., 2018). We need better systems to watch how well the vaccines are working. We also need to find people whose protection is fading and check if they need booster shots. This is even more important for people who are at higher risk. Vaccination has done a lot to fight HBV. But there's still more work to do. Leaders and health officials should focus on making new vaccines that can protect against new HBV types and last even longer. They also need to build better tracking systems to spot problems early and help people who might need extra protection. Making vaccination plans that fit each person better—like changing the schedule or giving extra shots for high-risk groups —can make programs even stronger. Countries and health groups around the world should work together to solve these new challenges. If we keep making better vaccines, better tracking systems, and smarter vaccine plans, we can protect all the progress we've made. And someday, we might finally get rid of HBV for good. Acknowledgments Thanks to Dr. Liu in this project team for collecting and combing the literature during the study. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Ahonen A., Zhang Y., Marček T., Lumley J., Johnson D., Guris D., and Wilck M., 2022, Demonstration of durable hepatitis B immune memory in children vaccinated with a DTaP5-IPV-HepB-Hib infant-toddler series 7 to 8 years previously, Human Vaccines & Immunotherapeutics, 18(1): 2031482. https://doi.org/10.1080/21645515.2022.2073747 Buti M., Viladomiu L., Jardí R., Olmos A., Rodríguez J., Bartolomé J., Esteban R., and Guardia J., 1992, Long-term immunogenicity and efficacy of hepatitis B vaccine in hemodialysis patients, American Journal of Nephrology, 12(3): 144-147. https://doi.org/10.1159/000168436 Chaiwarith R., Praparattanapan J., Kotarathititum W., Wipasa J., Chaiklang K., and Supparatpinyo K., 2019, Higher rate of long-term serologic response of four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: 4-year follow-up of a randomised controlled trial, AIDS Research and Therapy, 16. https://doi.org/10.1186/s12981-019-0249-8
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Journal of Vaccine Research 2024, Vol.14, No.6, 287-296 http://medscipublisher.com/index.php/jvr 287 Research Insight Open Access Efficacy of Combined Measles, Mumps, and Rubella Vaccines Jianbang Chen Huahai Pharmaceutical Co., Ltd., Taizhou, 317099, Zhejiang, China Corresponding author email: chejb@qq.com Journal of Vaccine Research, 2024, Vol.14, No.6 doi: 10.5376/jvr.2024.14.0027 Received: 20 Sep., 2024 Accepted: 31 Oct., 2024 Published: 28 Nov., 2024 Copyright © 2024 Chen, 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: Chen J.B., 2024, Efficacy of combined measles, mumps, and rubella vaccines, Journal of Vaccine Research, 14(6): 287-296 (doi: 10.5376/jvr.2024.14.0027) Abstract The combined measles, mumps, and rubella (MMR) vaccine has greatly helped reduce cases and deaths from these three diseases since it was introduced. However, some factors can affect how well the vaccine works. These include differences in individual immune response, low vaccine coverage in some areas, and changes in the viruses themselves. This study looks at how the MMR vaccine works, how effective it is in real-world use, and its impact on public health. It also discusses the main reasons that can affect vaccine success and suggests ways to improve vaccination strategies in the future. The results show that the MMR vaccine works very well to prevent measles, mumps, and rubella. The protection rate for measles and rubella is about 95%~99%. The protection against mumps is also good, but it may be a bit lower for some types of the virus. Having high vaccination rates is very important for reaching herd immunity and stopping the spread of these diseases. Many countries have greatly reduced outbreaks through their vaccination programs. The MMR vaccine is generally safe. Most people only have mild side effects like fever or rash. Serious side effects are very rare. The benefits of getting vaccinated are much greater than the risks of not being vaccinated. The MMR vaccine is still one of the best tools we have to control and prevent these diseases. Better virus tracking, new types of combined vaccines, and personalized vaccination plans could help make the vaccine even more effective. Raising public awareness about the importance of vaccines is also key to increasing coverage and helping reach global disease elimination goals. Keywords Measles; Mumps; Rubella; Combined vaccine; Herd immunity 1 Introduction Measles, mumps, and rubella (MMR) are highly contagious viral diseases that remain a big challenge for public health around the world. Measles alone causes many serious health problems, especially in children. It can lead to pneumonia, brain swelling (encephalitis), and even death (Tischer and Gerike, 2000; Povey et al., 2019). Mumps can cause complications like meningitis, swollen testicles (orchitis), and hearing loss. Rubella is especially dangerous for pregnant women because it can cause congenital rubella syndrome (CRS), which leads to birth defects or miscarriage (Marin et al., 2010). These diseases cause a heavy burden on health systems globally. Vaccination has been the best way to control and prevent them. It lowers the number of cases, reduces the spread of infection, and helps prevent serious health complications (Tischer and Gerike, 2000; Davidkin et al., 2008). The combined MMR vaccine was developed to make immunization easier and to improve coverage. The first combined MMR vaccine was licensed in the United States in 1971. Since then, many countries have started using it (Marin et al., 2010). The introduction of this vaccine was an important step in public health and helped greatly reduce the number of measles, mumps, and rubella cases. The combined vaccine has several benefits. It reduces the number of shots needed, helps more people complete the vaccine schedule, and is more cost-effective (Czajka et al., 2009; Bonanni et al., 2019). The MMR vaccine also provides strong and long-lasting protection. Studies show that most people stay immune for many years after getting vaccinated (Davidkin et al., 2008; Yhu-Chering et al., 2019). This study aims to review how well the MMR vaccine works to prevent these three diseases. It will look at how the vaccine helps stop the spread of infection, its success in reducing outbreaks, and the challenges of keeping
Journal of Vaccine Research 2024, Vol.14, No.6, 287-296 http://medscipublisher.com/index.php/jvr 288 vaccination rates high. The goal is to give a clear view of why the MMR vaccine remains a key part of protecting public health. 2 Mechanism of Action of the MMR Vaccine 2.1 Measles, mumps, and rubella Measles, mumps, and rubella are serious viral diseases, and each has its own symptoms. Measles usually starts with a high fever, cough, runny nose, and red, watery eyes. A red rash often appears a few days later, beginning on the face and then spreading over the body (Figure 1) (Destefano and Shimabukuro, 2019). Measles can cause problems like ear infections, diarrhea, pneumonia, and brain swelling (encephalitis). In some cases, these can lead to long-term health issues or death. Figure 1 Symptoms of measles in children (Adopted from Destefano and Shimabukuro, 2019) Image caption: a: Child with characteristic red, blotchy rash on third day of the measles rash; b: Koplik spots on the soft palate and oropharynx due to pre-eruptive measles on day 3 of the illness (Adopted from Destefano and Shimabukuro, 2019) Mumps often causes swollen, painful salivary glands under the ears or jaw. Other signs include fever, headache, muscle pain, tiredness, and loss of appetite. Some people may also develop meningitis, encephalitis, hearing loss, or swelling of the testicles or ovaries, which can sometimes lead to infertility (Di Pietrantonj et al., 2020). Rubella, or German measles, usually causes a mild fever, headache, and a rash that starts on the face and spreads to the body. It may also cause swollen lymph nodes, cough, or a runny nose. Rubella is often mild in children but very dangerous for pregnant women. If a woman gets rubella during pregnancy, it can cause serious birth defects like heart problems, hearing and vision loss, or developmental delays in the baby. The MMR vaccine works well to prevent these diseases and their complications. After the full vaccine doses, the protection rates are about 95%~96% for measles, 72%~86% for mumps, and 89% for rubella (Di Pietrantonj et al., 2020). 2.2 Basic mechanism of immune response The MMR vaccine helps the body build protection by teaching the immune system how to fight these viruses. The vaccine contains live but weakened forms of the measles, mumps, and rubella viruses. After the vaccine is given, the body reacts by making antibodies. These are special proteins that can block the viruses. The immune system also uses T cells, which help find and destroy infected cells. B cells, another type of immune cell, are the ones that produce the antibodies (Tischer and Gerike, 2000; Davidkin et al., 2008; Prymula et al., 2021; Jiang, 2024). Both the T cells (cellular immunity) and the B cells (humoral immunity) work together to protect the body. This strong immune response is what makes the MMR vaccine so effective against measles, mumps, and rubella. 2.3 Composition of the MMR vaccine The MMR vaccine contains live but weakened (attenuated) viruses for measles, mumps, and rubella. Each virus strain is chosen carefully to make sure the vaccine is both safe and effective. The measles part usually comes from the Edmonston-Zagreb strain. The mumps part uses the Jeryl Lynn strain, and the rubella part uses the RA 27/3 strain (Tischer and Gerike, 2000; Czajka et al., 2009; Bonanni et al., 2019).
Journal of Vaccine Research 2024, Vol.14, No.6, 287-296 http://medscipublisher.com/index.php/jvr 289 These vaccine strains are able to trigger a strong immune response. Studies show that the measles part of the vaccine gives high and long-lasting protection, with many people staying immune for years (Davidkin et al., 2008; Prymula et al., 2021). The mumps and rubella parts also work well, although in some cases the immune response to mumps may be a bit lower (Tischer and Gerike, 2000; McLean et al., 2018). 2.4 Immune response to vaccination The MMR vaccine helps the body build both humoral and cellular immunity. After the vaccine is given, the weakened viruses in the shot start to copy themselves inside the body. This activates the immune system. B cells make special proteins called antibodies. These antibodies attack and block the measles, mumps, and rubella viruses. This is called humoral immunity. At the same time, T cells are also activated. They help find and destroy infected cells. This is called cellular immunity (Tischer and Gerike, 2000; Davidkin et al., 2008; Prymula et al., 2021). The protection from the MMR vaccine lasts a long time. One study showed that many people still had strong antibody levels 20 years after getting the vaccine (Davidkin et al., 2008). But over time, these antibody levels can go down. Because of this, booster shots may be needed to keep the best level of protection (Tischer and Gerike, 2000; Pebody et al., 2002). 3 Clinical Efficacy of the MMR Vaccine 3.1 Efficacy against measles The MMR vaccine works very well to prevent measles. Many studies show that the vaccine leads to high levels of protection. One study found that the seroconversion rate for measles was 100% in both groups of children, no matter what age they got their first dose (He et al., 2014). Another study compared two different MMR vaccines and found that children who received the "Priorix" vaccine had higher levels of anti-measles antibodies than those who got "Triviraten" (Crovari et al., 2000). These antibodies stayed at high levels, with no major drop one year after vaccination. These results show that the MMR vaccine gives strong and long-lasting protection against measles. 3.2 Efficacy against mumps The protection from the MMR vaccine against mumps can vary, depending on which vaccine strain is used. A study from Spain found that children who got the "Vac triple MSD" vaccine had a much higher seroconversion rate for mumps than those who got "Triviraten" (81.1% vs. 14.3%) (Rojo et al., 2003). This shows that the type of vaccine strain makes a big difference. Another study found that mumps antibodies dropped a lot about 10 months after the first MMR dose. But giving a second dose helped restore high levels of protection (He et al., 2014). In a large trial in Italy, the "Priorix" vaccine again showed better results than "Triviraten" for mumps, with a seroconversion rate of 97.0% compared to 35.4% (Crovari et al., 2000). These studies suggest that while the MMR vaccine does protect against mumps, the strain of the vaccine and giving two doses are both very important for getting the best protection. 3.3 Efficacy against rubella The MMR vaccine is very effective in preventing rubella. A long-term study from Finland followed children for 15 years after they received the MMR vaccine. The results showed that 100% of the children had rubella antibodies after the first shot. Even after 15 years, 99% of them were still seropositive, which means their immunity stayed strong (Davidkin et al., 2000). Another study also found that children stayed fully protected against rubella for at least 10 years after getting the vaccine (Prymula et al., 2021). These studies show that the MMR vaccine gives long-lasting and reliable protection against rubella. 3.4 Overall efficacy The MMR vaccine provides strong overall protection against measles, mumps, and rubella. In Finland, after
Journal of Vaccine Research 2024, Vol.14, No.6, 287-296 http://medscipublisher.com/index.php/jvr 290 starting a two-dose MMR vaccination plan, the country was able to stop the spread of these diseases completely (Davidkin and Valle, 1998). This real-world success proves how well the vaccine works. The vaccine also helps prevent serious cases that need hospital care. One study showed that the MMR vaccine reduced hospitalizations for measles and mumps by 90%. The hazard ratio for these hospitalizations was 0.10, which means a much lower risk for vaccinated people (La Torre et al., 2017). There is also some research suggesting that the MMR vaccine might help reduce the severity of COVID-19 symptoms, showing possible cross-protection against other viruses (Table 1) (Fedrizzi et al., 2021). Table 1 Hospitalizations for measles and mumps, all infectious diseases and respiratory diseases for all MMR vaccine doses (Adopted from La Torre et al., 2017) Vaccine Measles N (%) Mumps N (%) Measles and MumpsN(%) All infectious diseases N (%) All respiratory diseases N (%) Nodose 9 (0.4) 1 (0.04) 10 (0.4) 262 (11.4) 424 (18.4) 1 dose 3 (0.06) 1 (0.01) 4 (0.1) 82 (1.5) 202 (3.7) 2 doses 0 (0) 0 (0) 0 (0) 70 (2.1) 183 (5.5) Total 12 (0.1) 2 (0.01) 14 (0.1) 414 (3.8) 809 (7.4) p <0.001 Ns <0.001 <0.001 <0.001 The MMR vaccine has clearly helped lower sickness and death from these three diseases. High rates of long-lasting immunity have greatly cut down the number of cases. The success in Finland, where measles, mumps, and rubella were eliminated after using the vaccine, is a good example of its power to control these diseases (Davidkin and Valle, 1998). The vaccine also helps reduce hospital stays for infections, including some lung diseases, which shows its wider health benefits (La Torre et al., 2017). Overall, the MMR vaccine has played a key role in improving public health and lowering the burden of these diseases worldwide. 4 Factors Influencing the Efficacy of the MMR Vaccine 4.1 Vaccine coverage and immunization strategies The success of the MMR vaccine depends a lot on how many people get vaccinated. High coverage is very important to stop the spread of measles, mumps, and rubella. For example, in Finland, a two-dose vaccine program with 97%~98% coverage helped fully eliminate these diseases (Davidkin and Valle, 1998). On the other hand, if not enough people get the vaccine, outbreaks can still happen. Low coverage reduces herd immunity and makes the vaccine less effective at protecting the whole community. 4.2 Individual differences and immune response The body’s response to the MMR vaccine can be different from person to person. Age, nutrition, and immune health all play a role. Some studies show that giving the first dose at 8 months of age can work just as well as giving it at 12 months (He et al., 2014). This means there is some flexibility in when the first dose can be given. Children who are malnourished or have weak immune systems may not respond as well to the vaccine. These children might need special vaccination plans to make sure they get enough protection (Lalwani et al., 2015). 4.3 Impact of viral variants Different virus strains can affect how well the vaccine works, especially for mumps. Some studies found that children who got the MMR vaccine with the Urabe mumps strain had better antibody levels than those who got the Jeryl Lynn strain. This shows that the type of virus strain used in the vaccine matters. Because of this, it is important to keep checking for new virus variants and update the vaccines if needed. 4.4 Need for booster doses Studies show that getting more than one dose of the MMR vaccine gives better long-term protection. For example, in a 10-year study, children who got two doses of the MMRV vaccine stayed protected against varicella
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