Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

The COVID-19 Vaccine Safety Research Center: a cornerstone for strengthening safety evidence for COVID-19 vaccination in the Republic of Korea

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC’s initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC’s second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public.

Public Perception Towards Drug Abuse in South Korea: The Effects of Overconfidence and Affirmation

Objective@#The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse. @*Methods@#Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse. @*Results@#In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569). @*Conclusion@#The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024.This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.

A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA’s COVID-19 vaccination data and the National Health Insurance Service’s claims data. The CoVaSC’s 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Social Stigma and Discrimination Toward People With Drug Addiction: A National Survey in Korea

Objective@#This study aims to understand the attitudes, stigma, and discrimination of the general adult population toward drug addiction. @*Methods@#We conducted a cross-sectional nationwide survey with 1,020 Korean adults using an Internet web-based panel. Self-reported data were collected on demographics, experience with substance abuse, perceptions of narcotic analgesic use, beliefs about the legalization of cannabis use, coping with substance abuse and addiction, and perceptions of drug risks. All statistical analysis in this study utilized the IBM SPSS Statistics 26 program. @*Results@#In this study, 1.6% of the participants reported abuse of opioid analgesics, 88.0% reported negative perceptions of drug addiction, and 76.9% reported agreeing to unfair treatment of drug addicts. Logistic regression analysis found that perceived stigma was more prevalent among women (odd ratio [OR]=2.087, p<0.01), old adults (OR=1.939, p<0.01), those with no personal experience of opioid misuse (OR=8.172, p<0.05), and those who were non-smoking (OR=2.011, p<0.01). In addition, the discriminatory attitude was more prevalent among participants with higher income (OR=1.989, p<0.001) and those who are non-smoking (OR=1.608, p<0.05). @*Conclusion@#This study provides information and guidelines for public intervention in drug addiction by identifying factors influencing social stigma and discriminatory behaviors toward drug addiction. The findings suggest that education on drug addiction prevention for the general adult population is necessary, and this education should include knowledge on coping with drug addiction and reducing stigma and discrimination toward drug addicts.

Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy

Background@#and Purpose Data regarding the effects of cannabidiol (CBD) on the quality of life (QOL) are currently inadequate. We assessed the QOL of pediatric patients with epilepsy who were treated with CBD. @*Methods@#This prospective, open-label study included pediatric and adolescent patients (aged 2–18 years) with Dravet syndrome or Lennox-Gastaut syndrome. Oral CBD was administered at 10 mg/kg/day. The Korean version of the Quality Of Life in Childhood Epilepsy (QOLCE) questionnaire was administered when CBD treatment began and again after 6 months. Adaptive behavior was measured using the Korean versions of the Child Behavior Checklist (K-CBCL) and the second edition of the Vineland Adaptive Behavior Scales (Vineland-II). @*Results@#This study included 41 patients (11 with Dravet syndrome and 30 with LennoxGastaut syndrome), of which 25 were male. The median age was 4.1 years. After 6 months, 26.8% (11/41) of patients experienced a ≥50% reduction in the number of seizures. The total score for the QOLCE questionnaire did not change from baseline to after 6 months of CBD treatment (85.71±39.65 vs. 83.12±48.01, respectively; p=0.630). The score in the motor skills domain of Vineland-II reduced from 48.67±13.43 at baseline to 45.18±14.08 after 6 months of treatment (p=0.005). No other Vineland-II scores and no K-CBCL scores had changed after 6 months of CBD treatment. @*Conclusions@#CBD is an efficacious antiseizure drug used to treat Dravet syndrome and Lennox-Gastaut syndrome. However, it did not improve the patient QOL in our study, possibly because all of our patients had profound intellectual disabilities.

Cannabidiol for Treating LennoxGastaut Syndrome and Dravet Syndrome in Korea

Background@#For the first time in Korea, we aimed to study the efficacy and safety of cannabidiol (CBD), which is emerging as a new alternative in treating epileptic encephalopathies. @*Methods@#This study was conducted retrospectively with patients between the ages of 2–18 years diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) were enrolled from March to October 2019, who visited outpatient unit at 3 and 6 months to evaluate medication efficacy and safety based on caregiver reporting. Additional evaluations, such as electroencephalogram and blood tests, were conducted at each period also. CBD was administered orally at a starting dose of 5 mg/kg/day, and was maintained at 10 mg/kg/day. @*Results@#We analyzed 34 patients in the LGS group and 10 patients in the DS group between the ages of 1.2–15.8 years. In the 3-month evaluation, the overall reduction of seizure frequency in the LGS group was 52.9% (>50% reduction in 32.3% of the cases), and 29.4% in the 6-month evaluation (more than 50% reduction in 20.6%). In DS group, the reduction of seizure frequency by more than 50% was 30% and 20% in the 3-month and 6-month evaluation, respectively. Good outcomes were defined as the reduction of seizure frequency by more than 50% and similar results were observed in both LGS and DS groups. Adverse events were reported in 36.3% of total patients of which most common adverse events were gastrointestinal problems. However, no life-threatening adverse event was reported in both LGS and DS during the observation period. @*Conclusion@#In this first Korean study, CBD was safe and tolerable for use and could be expected to potentially reduce the seizure frequency in pediatric patients with LGS or DS.

Cannabidiol for Treating LennoxGastaut Syndrome and Dravet Syndrome in Korea

Background@#For the first time in Korea, we aimed to study the efficacy and safety of cannabidiol (CBD), which is emerging as a new alternative in treating epileptic encephalopathies. @*Methods@#This study was conducted retrospectively with patients between the ages of 2–18 years diagnosed with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) were enrolled from March to October 2019, who visited outpatient unit at 3 and 6 months to evaluate medication efficacy and safety based on caregiver reporting. Additional evaluations, such as electroencephalogram and blood tests, were conducted at each period also. CBD was administered orally at a starting dose of 5 mg/kg/day, and was maintained at 10 mg/kg/day. @*Results@#We analyzed 34 patients in the LGS group and 10 patients in the DS group between the ages of 1.2–15.8 years. In the 3-month evaluation, the overall reduction of seizure frequency in the LGS group was 52.9% (>50% reduction in 32.3% of the cases), and 29.4% in the 6-month evaluation (more than 50% reduction in 20.6%). In DS group, the reduction of seizure frequency by more than 50% was 30% and 20% in the 3-month and 6-month evaluation, respectively. Good outcomes were defined as the reduction of seizure frequency by more than 50% and similar results were observed in both LGS and DS groups. Adverse events were reported in 36.3% of total patients of which most common adverse events were gastrointestinal problems. However, no life-threatening adverse event was reported in both LGS and DS during the observation period. @*Conclusion@#In this first Korean study, CBD was safe and tolerable for use and could be expected to potentially reduce the seizure frequency in pediatric patients with LGS or DS.

Detection and genetic analysis of zoonotic hepatitis E virus, rotavirus, and sapovirus in pigs

The zoonotic transmission of viral diseases to humans is a serious public health concern. Pigs are frequently a major reservoir for several zoonotic viral diseases. Therefore, periodic surveillance is needed to determine the infection rates of zoonotic diseases in domestic pigs. Hepatitis E virus (HEV), rotavirus, sapovirus (SaV), and norovirus (NoV) are potential zoonotic viruses. In this study, 296 fecal samples were collected from weaned piglets and growing pigs in 13 swine farms, and the viral RNA was extracted. Partial viral genomes were amplified by reverse transcription-polymerase chain reaction (PCR) or nested-PCR using virusspecific primer sets under different PCR conditions. HEV-3, rotavirus A, and SaV genogoup 3 were detected from 11.5, 2.7, and 3.0% of the samples, respectively. On the other hand, NoV was not detected in any of the samples. Genetic analysis indicated that the nucleotide sequences of swine HEV-3 and rotavirus A detected in this study were closely related to those of human isolates. However, swine SaV was distant from the human strains. These results suggest that HEV-3 and rotavirus A can be transmitted from pigs to humans. Therefore, strict preventive measures should be implemented by workers in the swine industry to prevent infections with HEV-3 and rotavirus A excreted from pigs.

Educating Healthcare Professionals in Pharmacovigilance: Global Trends and Korea’s Status / 의학교육논단

This narrative review introduces global trends in pharmacovigilance (PV) education for healthcare professionals and the status of PV education in Korea. Proactive participation of healthcare professionals, including physicians, pharmacists, and nurses in reporting suspected adverse events is the main driving force for effective operation of the spontaneous adverse event reporting system database, which in turn facilitates early safety signal detection of otherwise unknown suspected adverse events. The World Health Organization recognizes PV education curriculum as a key aspect in promoting awareness of PV and adverse event reporting among healthcare professionals, and multiple studies have demonstrated that PV educational interventions for healthcare professionals have increased overall adverse event reporting. Considering the global trends in PV education, the curriculum in Korean universities still has room for improvement in promoting PV obligation among future healthcare professionals. Further research is needed to develop PV education curriculum. We suggest a three-step project for innovating PV education in Korea to meet the global PV educational standards: a survey to gauge current PV competencies among healthcare professionals, reform of current PV academic curriculum, and evaluation and fine-tuning of the reformed curriculum.

Issues on carcinogen contaminated antihypertensive drugs and constructing drug safety management system

European Medicines Agency withdrew valsartan from European market in July 2018 because it was contaminated with carcinogen, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). Medicines and Healthcare Products Regulatory Agency also found the same contamination and withdrew it from England market. US Food and Drug Administration followed the action after confirming its contamination. Ministry of Food and Drug Safety (MFDS) conducted testing all the valsartans at Korean market and withdrew some of them from market after confirming the contamination with NDMA. MFDS provided the pharmaceutical companies and laboratory institutions with the manual for testing both NDMA and NDEA and educated relevant personnels. MFDS also evaluated the health impact of the contaminated valsartan on the hypertensive patients who took the valsartan, which was shown to be very low risk of additional cancer incidence. MFDS pronounced strengthening of the safety management for the raw materials of the medicines. For guaranteeing the safety of medicines, more comprehensive drug safety management system from developing new drugs to consuming the medicines should be established. For achieving such a goal, active participation of all the stakeholders of the medicines including governmental agencies including MFDS and Ministry of Health and Welfare, the National Assembly, healthcare professionals, pharmaceutical companies, mass media, and general population including patients should be needed.

Nationwide Incidence of Acute Angle Closure Glaucoma in Korea from 2011 to 2015

Issues on carcinogen contaminated antihypertensive drugs and constructing drug safety management system

European Medicines Agency withdrew valsartan from European market in July 2018 because it was contaminated with carcinogen, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). Medicines and Healthcare Products Regulatory Agency also found the same contamination and withdrew it from England market. US Food and Drug Administration followed the action after confirming its contamination. Ministry of Food and Drug Safety (MFDS) conducted testing all the valsartans at Korean market and withdrew some of them from market after confirming the contamination with NDMA. MFDS provided the pharmaceutical companies and laboratory institutions with the manual for testing both NDMA and NDEA and educated relevant personnels. MFDS also evaluated the health impact of the contaminated valsartan on the hypertensive patients who took the valsartan, which was shown to be very low risk of additional cancer incidence. MFDS pronounced strengthening of the safety management for the raw materials of the medicines. For guaranteeing the safety of medicines, more comprehensive drug safety management system from developing new drugs to consuming the medicines should be established. For achieving such a goal, active participation of all the stakeholders of the medicines including governmental agencies including MFDS and Ministry of Health and Welfare, the National Assembly, healthcare professionals, pharmaceutical companies, mass media, and general population including patients should be needed.

Epidemiological Impact of the Korean National Immunization Program on Varicella Incidence

The number of reported varicella cases is continuously increasing in Korea; however, associated medical utilization is declining. The ratio between varicella insurance claims and reports of passive infectious disease surveillance has gradually increased to > 80% since the second half of 2017. The recent increase in reported varicella cases is influenced by improved reporting. We calculated the varicella incidence and cumulative incidence in each birth cohort according to age. The cumulative incidence rate among children aged < 6 years in the birth cohort born after the National Immunization Program introduced the varicella vaccine was about 60% lower than among children born before

Detection of hepatitis E virus genotypes 3 and 4 in pig farms in Korea

Zoonotic transmission of hepatitis E virus (HEV) is mostly mediated by HEV-3 and HEV-4 genotypes, and domestic pigs are an important reservoir of these genotypes. A survey of 14 pig farms in Korea revealed HEV RNA in 30 of 148 (20.3%) fecal samples. HEV-3a and HEV-4c subtypes were identified in five pig farms (35.7%) and two pig farms (14.3%), respectively. Phylogenetic analysis indicated that the isolated HEV strains were closely related to previously reported zoonotic strains in Korea. The results of the genetic analysis partially explain the possible source of the zoonotic transmission of HEV to humans in Korea.

Hypertension Risk with Abacavir Use among HIV-Infected Individuals: A Nationwide Cohort Study

PURPOSE: A high risk of cardiovascular disease (CVD) is reported for HIV-infected individuals. While a link between abacavir and CVD risk is suggested, an association between abacavir and hypertension remains unclear. This study evaluated hypertension risk with abacavir use in comparison to non-abacavir antiretroviral treatment (ART). MATERIALS AND METHODS: From a nationwide cohort of HIV-infected individuals on their initial ART, 6493 who were free of hypertension at baseline were analyzed. The use of ART was treated as a time-varying covariate measured as a daily unit. Incidence rate of hypertension was calculated, and Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) with 95% confidence interval (CI) of incident hypertension overall and among subgroups. RESULTS: From the 6493 participants, 24072 person-years (PY) of follow-up were contributed during 2008–2016. The incidence rates of hypertension were 4.6 and 3.6 per 100 PY for abacavir and non-abacavir ART users, respectively. The population attributable fraction of abacavir use on hypertension was 12%. Abacavir exposure did not elevate the risk of hypertension among overall study population [HR, 1.2 (95% CI, 1.0–1.4), p=0.061]. However, those with poor ART adherence, defined as a medication possession ratio < 50% [HR, 1.9 (95% CI, 1.5–2.4), p < 0.0001] or requiring prophylactic antibiotics [HR, 1.2 (95% CI, 1.0–1.3), p=0.023], were at risk of hypertension induced by abacavir, as were men, individuals aged ≥40 years, and patients visiting tertiary hospitals in urban areas. CONCLUSION: When present, poor ART adherence, requiring prophylactic antibiotics, male sex, and older age may warrant additional concern for hypertension in patients treated with abacavir.

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016

BACKGROUND: To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. METHODS: We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. RESULTS: The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. CONCLUSION: The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

High Level Physical Activity and Prevalence of Cardiovascular Disease Using the Korea National Health and Nutrition Examination Survey Data, 2007-2013 / 예방의학회지

OBJECTIVES: The purpose of our study was to evaluate the association between the intensity of physical activity (PA) and prevalence of cardiovascular disease (CVD) using Korean representative data. METHODS: We analyzed 39 804 participant data from the Korea National Health and Nutrition Examination Survey, 2007-2013. Exposure variable was three levels of PA (low, medium, and high) in a week, and outcome variable was prevalence of CVD based on patient self-recognition and doctor's diagnosis. Complex logistic regression analysis was performed to evaluate the relationship between level of PA and CVD adjusted by body mass index, hypertension, hypercholesterolemia, diabetes mellitus, stress recognition, household income, smoking, and current drinking. The indices of association w ere estimated as crude prevalence odds ratio (POR), adjusted POR, and their 95% confidence interval (CI). All statistical analyzes were performed using complex sample analysis procedure of the SPSS version 23.0. RESULTS: When all variables were adjusted, only high level PA in women showed a significant association with stroke (adjusted POR by patient's self-recognition, 0.57; 95% CI, 0.32 to 0.99, adjusted POR by doctor's diagnosis, 0.55; 95% CI, 0.34 to 0.87) and CVD (adjusted POR by doctor's diagnosis, 0.68; 95% CI, 0.48 to 0.96). CONCLUSIONS: High level PA in women has a significant reverse association with prevalence of stroke and CVD in Korea. Further study for elucidating the mechanism will be needed.

Evaluation of immunocontraceptive vaccine composed of gonadotropin-releasing hormone conjugated with granulocyte-macrophage colony-stimulating factor in male rats

Surgical castration performed to reduce male-associated problems results in pain and microbial infections in male animals. Therefore, immunocontraception, which is mediated by the animal's own antibodies against reproductive hormones, has been recommended as an alternative to surgical castration when considering the animal's welfare. In this study, a new immunocontraceptive vaccine composed of six tandem copies of gonadotropin-releasing hormone (GnRH) fused to rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed, and its efficacy was evaluated in male rats. Three different doses (10, 50, and 100 µg) of recombinant GM-CSF–GnRH protein were injected three times at intervals of two weeks into male rats. The rats vaccinated with three doses of GM-CSF–GnRH produced a significantly higher level of antibodies against GnRH than that in the negative control rats. Severe atrophy of gonads was observed in rats vaccinated with three doses of GM-CSF–GnRH but not in the negative control rats. The results reveal that the new GnRH vaccine conjugated with rat GM-CSF induces efficient immunocontraception in male rats. This formulation of the immunocontraceptive vaccine would be applicable to both domestic and pet male animals.