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Abstract Background Typhoid fever is commonly found until today, especially in developing countries. It has fatal complications and measures must be taken to reduce the incidence of typhoid. Vaccinations are a key factor in prevention. This is a phase II randomized observer-blind clinical trial on a novel Vi-DT conjugate vaccine on 200 subjects 12 to 40 years of age. Methods Subjects were screened for eligibility after which a blood sample was taken and one dose of vaccine was administered. Investigational vaccine used was Vi-DT and control was Vi-PS. Twenty-eight days after vaccination, subjects visited for providing blood sample to assess immunogenicity and were asked about local and systemic adverse reactions that occurred in the first 28 days. Results Subjects had minor adverse reactions. Pain was the most common local reaction. Muscle pain was the most common systemic reaction. There were no serious adverse events up to 28 days post vaccination. Seroconversion rates were 100% in the Vi-DT group and 95.96% in the Vi-PS group. Post vaccination GMTs were increased in both groups but it was significantly higher in the Vi-DT group (p

Objective: Detection of high-risk human papillomavirus (hr-HPV) in urine specimens has been introduced recently and a new local PCR kit has been developed in Indonesia (CerviScan, Bio Farma). The objective of this study was to obtain the accuracy of hr-HPV DNA testing using the new kit (CerviScan, Bio Farma) on urine specimens against the gold standard on cervical swabs. Method: Adult women (aged 20–50 years) underwent routine general check-up or Pap test were enrolled between July and September 2022. Pairs of urine and cervical swab specimens were obtained from all subjects. HPV-DNA tests were performed using the new local PCR kit (CerviScan, Bio Farma) and the standard procedure (COBAS® 6800 HPV, Roche Molecular System). Direct sequencing was added whenever there were dispute results between the two methods. Agreement between both methods was tested using Kappa statistics. Diagnostic performance test was done on CerviScan. Results: A total of 876 women completed the examination. Agreement between CerviScan and COBAS® 6800 was substantial (K=0.662; p

Adolescents are vulnerable to Coronavirus disease 2019 (COVID-19) infections; thus, their antibodies should be maintained above the protective value. This study aimed to evaluate the immune response and safety to the SARS-CoV-2 protein subunit recombinant vaccine (IndoVac®) as a heterologous booster dose against COVID-19 in Indonesian adolescents. This open-label prospective intervention study enrolled 150 clinically healthy adolescents aged 12–17 years who had received complete primary doses of the CoronaVac® vaccine from Garuda Primary Care Centres in Bandung City. The result of immunogenicity was presented with a 95% confidence interval (CI) and analyzed with t-tests from 14 days and 3, 6, and 12 months. The neutralizing antibody geometric mean titers (GMTs) (IU/mL) at baseline and 14 days after booster dose were 303.26 and 2661.2, respectively. The geometric mean fold rises (GMFR) at 3, 6, and 12 months after booster dose were 6.67 (5.217–8.536), 3.87 (3.068–4.886), and 2.87 (2.232–3.685), respectively. Both the neutralizing antibody and IgG antibody were markedly higher in the adolescents than in the adults at every timepoint. The incidence rate of adverse effects (AEs) until 28 days after booster dose was 82.7%, with a higher number of local events reported. Most reported solicited AEs were local pain followed by myalgia with mild intensity. Unsolicited AEs varied with each of the incidence rates < 10%, mostly with mild intensity. Adverse events of special interest (AESI) were not observed. At the 12-month follow-up after the booster dose, four serious adverse events (SAEs) not related to investigational products and research procedures were noted. This study showed that IndoVac® has a favorable immunogenicity and safety profile as a booster in adolescents and that the antibody titer decreases over time.

Background: In order to fulfil the requirements of the national immunization program and sustain the production capacity of the monovalent Hepatitis B vaccine, this study aimed to assess the safety and immunogenicity of the recombinant Hepatitis B Vaccine (Bio Farma) using the new Hepatitis B bulk. Methods: This study was an experimental, randomized, double-blinded, and controlled Phase I clinical trial, with 100 healthy subjects divided into 50 adults and 50 adolescents. Subjects were randomly assigned to receive either the Bio Farma registered Recombinant Hepatitis B Vaccine (group A) or a new source of Hepatitis B bulk (group B). Subjects received one or three doses of vaccine, depending on the baseline anti-Hbs titer. Subjects were given diary cards to record solicited and unsolicited adverse events for 28 days following vaccination. Vaccine immunogenicity was assessed by measuring the level of HBsAg antibody titer elevation. Results: No serious adverse events were reported during clinical trials. The frequencies of adverse events were not significantly different between the two vaccine-randomized groups. The most immediately observed local reaction was local pain, reported by 35.7–42.8% of adults and 24.0–26.3% of adolescents, without any systemic reactions. Seroconversion in adults in group B reached 100% and 78.5% in group A, meanwhile in adolescent subjects in both groups it reached 100%. A substantial increase in geometric mean titer (GMT) was observed in the majority of subjects after immunization. Conclusion: Recombinant Hepatitis B Vaccine with a new source of HBsAg B bulk is safe, well tolerated, and highly immunogenic.

Background: COVID-19 is one of the most devastating pandemics of the 21st century. Vaccination is one of the most effective prevention methods in combating COVID-19, and one type of vaccine being developed was the protein subunit recombinant vaccine. We evaluated the efficacy of the CoV2-IB 0322 vaccine in Depok, Indonesia. Methods: This study aimed to assess the humoral and cellular immune response of the CoV2-IB 0322 vaccine compared to an active control vaccine (COVOVAX™ Vaccine). A total of 120 subjects were enrolled and randomized into two groups, with 60 subjects in each group. Participants received either two doses of the CoV2-IB 0322 vaccine or two doses of the control vaccine with a 28-day interval between doses. Safety assessments were conducted through onsite monitoring and participant-reported adverse events. Immunogenicity was evaluated by measuring IgG anti-RBD SARS-CoV-2 and IgG-neutralizing antibodies. Cellular immunity was assessed by specific T-cell responses. Whole blood samples were collected at baseline, 14 days, 6 months, and 12 months after the second dose for cellular immunity evaluation. Results: Both vaccines showed high seropositive rates, with neutralizing antibody and IgG titers peaking 14 days after the second dose and declining by 12 months. The seroconversion rate of anti-S IgG was 100% in both groups, but the rate of neutralizing antibody seroconversion was lower in the CoV2-IB 0322 vaccine group at 14 days after the second dose (p = 0.004). The CoV2-IB 0322 vaccine showed higher IgG GMT levels 6 and 12 months after the second dose (p < 0.001 and p = 0.01). T-cell responses, evaluated by IFN-γ, IL-2, and IL-4 production by CD4+ and CD8+ T-cells, showed similar results without significant differences between both groups, except for %IL-2/CD4+ cells 6 months after the second dose (p = 0.038). Conclusion: Both vaccines showed comparable B- and T-cell immunological response that diminish over time.

Patients with Type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) face an increased risk of morbidity and mortality after influenza infection. Several studies have shown that the influenza vaccine effectively prevents morbidity and mortality in T2DM patients. However, there has been limited research aimed at assessing the effectiveness of the trivalent influenza vaccine in T2DM–CKD patients. This study aimed to identify Geometric Mean Titers (GMTs), seroprotection, seroconversion, safety, and efficacy. This open-label clinical trial was conducted at AMC Hospital in Bandung, West Java, Indonesia between June 2021 and July 2022. The study subjects consisted of 41 T2DM and 26 T2DM–CKD patients who were administered the trivalent influenza vaccine. There was a significant difference in the average age, with the T2DM–CKD patients being older. Median titers post-vaccination for the B/Washington virus were higher in the T2DM patients compared to the T2DM–CKD patients, and this difference was statistically significant. A majority, comprising 75.6% of the T2DM and 80.8% of the T2DM–CKD patients monitored post-influenza-vaccination, did not experience any adverse reactions. The most common reaction was the sensation of fever, with incidence rates of 12.2% in the T2DM patients and 15.4% in the T2DM–CKD patients. Furthermore, we observed that the incidence of Influenza-like Illness was highest at 7.3% in the T2DM patients and 7.7% in the T2DM–CKD patients. The trivalent influenza vaccine demonstrated equivalent safety and effectiveness in both groups.

One of the newest strategies developed by the Global Influenza Strategy has been to broaden the composition of the current influenza vaccine formulations from trivalent products to quadrivalent products. This study aimed to assess the immunogenicity and safety of Quadrivalent Influenza HA vaccine (QIV) compared with Trivalent Influenza HA vaccine (TIV) and to evaluate three consecutive batches of QIV equivalence in Indonesian children and adults. This was an experimental, randomized, double blind, four arm parallel group bridging study involving unprimed healthy children and adults aged 9–40 years. A total of 540 subjects were enrolled in this study and randomized into four arm groups. Each subject received one dose of TIV or QIV with three different batch codes. Serology tests were performed at baseline and 28 days after vaccination. Hemagglutination inhibition (HI) antibody titers were analyzed for Geometric Mean Titer (GMT), seroprotection, and seroconversion rates. Solicited, unsolicited, and serious adverse events were observed up to 28 days after vaccination. A total of 537 subjects completed the study per protocol and were analyzed for immunogenicity criteria. All randomized subjects were analyzed for safety criteria. The percentage of the subjects with anti-HI titer ≥1:40 28 days after QIV vaccination was 99.5% for A/H1N1; 99.5% for A/H3N2; 93.1% for B/Texas, and 99.0% for B/Phuket. The seroprotection, GMT, and seroconversion rates of QIV were not significantly different from those of TIV for the common vaccine strains (p > 0.01) and were significantly different from those of TIV for the added B/Phuket strains (p < 0.01). Most solicited injection-site and systemic reactions with either vaccine were mild to moderate and resolved within a few days. Antibody response to QIV were equivalence among vaccine batches and comparable between age groups for each of the 4 strains. QIV was immunogenic and well-tolerated and had immunogenicity and safety profiles compared with TIV for all common strains. The immunogenicity of the three batches of QIV was equivalent for the four strains. Trial registration. Clinical Trial registration: NCT03336593.

Abstract Background Typhoid fever caused by Salmonella enteric serovar Typhi (S. Typhi) is a common cause of morbidity in the world. In 2017, 14.3 million cases of Typhoid and paratyphoid fever occurred globally. School age children between 3 to 19 years old are the most affected. Poor sanitation and multi drug resistance have increased the need for vaccines to reduce the global burden of disease. Based on previous trials, typhoid conjugate vaccines have longer- lasting protection, higher efficacy, require fewer doses and are suitable from infancy that allows them to be incorporated into the routine immunization program. Our previous phase I trial proved that a novel Vi-DT typhoid conjugate vaccine is safe and immunogenic in subjects 2–5 and 18–40 years. Our phase II trial consisted of subjects 6 months to 40 years. Our previously published paper on subjects 6 to

Introduction: World Health Organization estimates the annual global incidence of typhoid fever at 11-21 million cases and approximately 128 000 to 161 000 deaths. The currently used Vi-polysaccharides (Vi-PS) vaccines have been proven to be safe and efficacious in children 2 years and above. However, poor immunogenicity of Vi-PS was observed in children below 2 years of age. This Phase II study is the continuation of the previously published Phase I study that aims to evaluate the safety and immunogenicity of a novel Vi-DT Typhoid Conjugate Vaccine (Bio Farma) in subjects 6 to

Satisfying the needs of the national immunization program requires maintaining diphtheria–tetanus–pertussis (DTP)–hepatitis B (HB)–Haemophilus influenza B (Hib) production. Therefore, new hepatitis B sources are needed. This study aimed to evaluate the immunogenicity of the DTP–HB–Hib vaccine (Bio Farma) that used a different source of hepatitis B. A prospective randomized, double-blind, bridging study was conducted. Subjects were divided into two groups with different batch numbers. Healthy infants 6–11 weeks of age at enrollment were immunized with three doses of the DTP–HB–Hib vaccine after a birth dose of hepatitis B vaccine. Blood samples were obtained prior to vaccination and 28 days after the third dose. Adverse events were recorded until 28 days after each dose. Of the 220 subjects, 205 (93.2%) completed the study protocol. The proportion of infants with anti-diphtheria and anti-tetanus titers ≥ 0.01 IU/mL was 100%, with anti-HBsAg titers ≥ 10 mIU/mL was 100%, and with Polyribosylribitol Phosphate-Tetanus Conjugate (PRP-TT) titers > 0.15 µg/mL was 96.1%. The pertussis response rate was 84.9%. No serious adverse events related to the study vaccine occurred. The three-dose DTP–HB–Hib vaccine (Bio Farma) is immunogenic, well tolerated, and suitable to replace licensed-equivalent vaccines.

AimTo investigate the effect of influenza vaccination with or without probiotic supplementation on the immune response and incidence of influenza-like illness (ILI) in the elderly.MethodsA randomized double-blind, placebo-controlled trial with a modified factorial design was conducted in 554 healthy elderly subjects aged 67 ± 5.6 (ranging from 60-90) years old in the Primary Health Care Center (Puskesmas area) of the Pulo Gadung District East Jakarta. Subjects received either a trivalent influenza vaccine or placebo at the start of the study, and a probiotic supplement (Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011) or a placebo for 6 months. Subjects were randomly assigned into four intervention groups: influenza vaccine and probiotics (n = 141), influenza vaccine and placebo (n = 136), placebo and probiotics (n = 140), and both placebo (n = 137). The primary outcome was ILI incidence within 6 months. The secondary outcomes were seroprotection and seroconversion rates at 1, 4, and 6 months after administering the interventions.ResultsThis study showed that the trivalent influenza vaccine increased seroprotection (RR 3.6 [95%CI 2.92-4.47]; pConclusionThe tested trivalent influenza vaccine significantly induced seroprotection and seroconversion in the vaccinated subjects, while probiotics administration did not influence these parameters. Vaccinated individuals displayed a similarly low ILI incidence as those in the Control Group. However, the observed trend towards a reduction of ILI incidence with probiotics supplementation warrants further assessments in a larger, at-risk population.Clinical trial registry numberNCT03695432.

Abstract Background The new combination of DTwP-HB-Hib vaccines has been developed in Indonesia following World Health Organization (WHO) recommendation and integrated into national immunization program. The aims of the study were to measure 1) antibody persistence 12–18 months after a primary series, 2) immune response and safety after a booster dose of DTwP-HB-Hib. Methods This was a multi-center, open-labeled, prospective, interventional study. Subjects who had received complete primary dose of DTwP-HB-Hib vaccine from the previous phase III trial were recruited in this trial. Subjects were given one dose of DTwP-HB-Hib (Pentabio®) booster at age 18–24 months old. Diphtheria, tetanus, pertussis, hepatitis B, Hemophilus influenza type B antibodies were measured before and after booster to determine antibody persistence and immune response. Vaccine adverse events were assessed immediately and monitored until 28 days after the booster recorded with parent’s diary cards. Results There were 396 subjects who completed the study. Increased proportion of seroprotected subjects from pre-booster to post-booster were noted in all vaccine antigens: 74.5 to 99.7% for diphtheria; 100 to 100% for tetanus; 40.4 to 95.5% for pertussis; 90.2 to 99.5% for hepatitis B; and 97.7 to 100% for Hib. Common systemic adverse events (AEs) were irritability (23.7–25%) and fever (39.9–45.2%). Local AEs such as redness, swelling, and induration were significantly less common in the thigh group (7.7, 11.3, and 7.1%) than in the deltoid group (28.9, 30.7, and 25%) (P

Background A phase II study of DTwP-HB-Hib vaccine compared to Hib (monovalent) vaccine given simultaneously with DTwP-HB vaccine has been done following the success of phase I study in infants, where the new DTwP-HB-Hib has excellent safety profiles and antibody responses in infants. Objective To evaluate the titer (quantity), avidity, and bactericidal capacity (quality of anti-polyribosylribitol phosphate/anti-PRP), of a new combined Bio Farma DTwP-HB-Hib (pentavalent) vaccine, compared to the Hib monovalent vaccine given simultaneously with the DTwP-HB vaccine (DTwP-HB+Hib). Methods The study was a prospective, randomized, open label, phase II trial. Subjects aged 6-11 weeks were allocated according to the randomization list. The pentavalent group received the DTwP-HB-Hib vaccine, while the monovalent group received the Hib monovalent and DTwP-HB vaccines separately. Immunizations were given in three doses with 28-day intervals. Blood specimens were taken before the first dose and 28 days after the last dose. We evaluated anti-PRP titers quantity (geometric mean antibody concentration/GMC) and seroprotection), followed by avidity and bactericidal (quality) testing. Titer and avidity of anti-PRP were tested using a modified version of the improved Phipps ELISA. Bactericidal capacity was evaluated using a Hib killing assay. Immune responses against other antigens in the vaccine were reported separately. Results One hundred five subjects in the pentavalent group and 106 subjects in the Hib monovalent group were tested for anti-PRP titers. Only 102 specimens for each group were available for bactericidal testing, due to insufficient volume for testing. Both vaccines induced similar anti-PRP titers, for GMC and seroprotection. Avidity increases were 82.9% and 76.4% in the pentavalent and Hib monovalent groups, respectively. Bactericidal activities were 94.1% and 89.2%, respectively. Both avidity and bactericidal activity were not significantly different between groups. Conclusion DTwP-HB-Hib vaccine induced anti-PRP quantity and quality comparable to those of the Hib monovalent vaccine given simultaneously with the DTwP-HB vaccine.

Latar belakang. Pemberian vaksin BCG pada bayi masih menjadi kebijakan pemerintah Indonesia dan WHO. Tujuan. Membandingkan keamanan dan konversi tuberkulin vaksin BCG strain Moskow dengan strain Pasteur. Metode. Tergabung dalam penelitian ini 220 bayi 0-1 bulan, kelompok A menerima vaksin BCG strain Pasteur, dan kelompok B menerima strain Moskow dengan randomisasi tersamar tunggal. Reaksi lokal dan sistemik yang timbul diamati hingga 30 hari pasca imunisasi. Uji tuberkulin dilakukan pada hari ke-90 pasca imunisasi, dengan pembacaan 48-72 jam kemudian. Hasil. Terdapat 205 anak berhasil menyelesaikan studi. Pembesaran kelenjar getah bening ditemukan pada kedua kelompok, masing-masing 2 bayi, yang sembuh sendiri tanpa pengobatan. Tidak ditemukan kejadian ikutan pasca imunisasi serius karena vaksin BCG. Jumlah bayi yang mempunyai jaringan parut dan konversi tuberkulin tidak berbeda signifikan, p=0,578 dan p=0,205 (p>0.05). Kesimpulan.Vaksin BCG strain Pasteur dan strain Moskow mempunyai profil keamanan dan konversi tuberkulin yang relatif sama.

IntroductionThere is a high global incidence of typhoid fever, with an annual mortality rate of 200,000 deaths. Typhoid fever also affects younger children, particularly in resource-limited settings in endemic countries. Typhoid vaccination is an important prevention tool against typhoid fever. However, the available polysaccharide typhoid vaccines are not recommended for children under 2 years of age. A new typhoid conjugate Vi-diphtheria toxoid (Vi-DT) vaccine has been developed for infant immunization. We aimed to define the safety and immunogenicity of the Vi-DT vaccine among adults and children in Indonesia.MethodsAn observational, blinded, comparative, randomized, phase I safety study in two age de-escalating cohorts was conducted in East Jakarta, Indonesia, from April 2017 to February 2018. We enrolled 100 healthy subjects in 2 age groups: adults and children (18-40 and 2-5 years old). These groups were randomized into study groups (Vi-DT vaccine), and comparator groups (Vi-polysaccharide (Vi-PS) vaccine and another additional vaccine) which was administered in 4 weeks apart. Subjects were followed up to six months.ResultOne hundred healthy adults and children subjects completed the study. The Vi-DT and Vi-PS vaccines showed no difference in terms of intensity of any immediate local and systemic events within 30 minutes post-vaccination. Overall, pain was the most common local reaction, and muscle pain was the most common systemic reaction in the first 72 hours. No serious adverse events were deemed related to vaccine administration. The first and second doses of the Vi-DT vaccine induced seroconversion and higher geometric mean titers (GMT) in all subjects compared to that of baseline. However, in terms of GMT, the second dose of Vi-DT did not induce a booster response.ConclusionThe Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

Post Marketing Surveillance should be conducted periodically to monitor whether the quality of marketed products is still favorable. The objectives of this study were to evaluate the protectiveness, local reaction, and systemic reaction after receiving booster dose of measles vaccine from different batch numbers. This study was a cohort study on elementary students in West Sumatra. Subjects from Agam District received measles vaccine with a batch number of 250210 while subjects from Limapuluh Kota District received measles vaccine with a batch number of 253080. Blood samples were collected before and 28 days after immunization. Antibody titers were measured using neutralization assay with a protective level of >200 mIU/mL. Local and systemic reactions were recorded within 28 days after immunization. The observation was held from November 2010 to March 2011 and involved 336 students: 170 students from Agam District and 166 students from Limapuluh Kota District. There were 1.2% students who experienced fever in the first three days after immunization, and 1(0.6%) student experienced mild fever 14 days after immunization. The most common local reaction was redness in the injection site, contributing approximately 14.48%. There were no serious adverse events after immunization. About 96.99% and 96.77% students were protected against measles 28 days after immunization in Agam and Limapuluh Kota Districts with an increase in GMT from 329.66 IU/mL to 983.43 IU/mL and from 198.00 IU/mL to 535.10 IU/mL (p=0.000). In conclusion, both measles vaccine batches show good safety and immune response.

Vaksin Hib mulai digunakan pada Pogram Imunisasi Nasional sejak tahun 2013 secara bertahap dan di seluruh Indonesia mulai tahun 2014 dalam bentuk vaksin kombinasi DTP/HB/Hib (Pentabio®), yang memberikan kekebalan terhadap difteria, pertusis, tetanus, hepatitis B, dan Haemophilus influenzae tipe b. Studi ini menilai reaksi sitemik, reaksi lokal, dan reaksi yang serius pascaimunisasi dengan Pentabio®. Sebanyak 4.000 bayi penerima vaksin Pentabio®bergabung dalam studi ini. Reaksi yang timbul dicatat pada kartu harian oleh petugas yang sudah dilatih. Vaksin Pentabio®yang diamati pada PMS ini menggunakan vaksin rutin dari Program Imunisasi Nasional dalam waktu pengamatan 28 hari di empat propinsi, yaitu Nusa Tenggara Barat, Bali, Yogyakarta, dan Jawa Barat pada periode Mei–Desember 2014. Sebanyak 3.978 data dapat dianalisis karena 22 di antaranya tidak memberikan informasi yang valid. Reaksi sistemik yang paling banyak timbul adalah demam 0,85% pada 30 menit pertama, dan meningkat menjadi 14,03% pada satu hari pascaimunisasi, kemudian sembuh pada hari berikutnya. Reaksi lokal yang paling sering timbul adalah nyeri pada tempat suntikan pada 67,6% subjek pada 30 menit setelah imunisasi, dan meningkat menjadi 87,23% pada 1 hari pascaimunisasi namun sembuh pada hari berikutnya. Mayoritas nyeri yang timbul adalah kategori ringan. Tidak ditemukan kejadian ikutan pascaimunisasi serius selama pengamatan. Simpulan, reaksi lokal dan sistemik pascaimunisasi dengan Pentabio® dapat ditoleransi pada bayi.

Td vaccine is given to provide protection to tetanus and diphtheria in children 7 years of age or above. The objectives of this study are to evaluate the reactions and immune response after 1 dose of Td vaccine. This study is a post marketing surveillance with a cohort design among elementary school students in East Java. Systemic and local reactions were recorded in diary cards untill 28 days after immunization. Blood was collected before and 28 days after immunization. Antibody titers were measured using double antigen ELISA with cut off protection rate >0,01 IU/ml. Observation were done between October 2010 to April 2011 which involved 2978 included 159 subjects for immune response group. In this study, fever was occured in 1,18%-2,45% subjects at the first three days with mild in intensity and resolved immediately without any medication. The most often local reaction was pain in 62,49% subjects at 30 minutes after injection, and increased to 83,38% at day 1 after immunization, and decreased the day after, with the intensity mostly were mild. No serious adverse reactions was found. 98,11% and 99,37% subjects were protected to diphtheria and tetanus, with the Geometric Mean Titer 1,2280 IU/mL (p=0,000) for anti-diphtheria and 10,6068 IU/mL (p=0.009) for anti-tetanus. In conclusion, Td vaccine is safe and immunogenic after 1 (one) dose in school age children, and there were no serious adverse event.