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Prevalence of hepatitis B surface antigen and antibody among health care employees in Negri Sembilan, Malaysia, 1989

Tan TC, Vadivale M, Ong CN

Asia Pac J Public Health, 1992;6(3):134-9.
PMID: 1342800 DOI: 10.1177/101053959200600303

This study was based on a hepatitis B screening program conducted in one of the states in Malaysia in 1989. The majority (84.6%) of the 2986 health employees were screened. One quarter (25%) was found to have serological markers for the Hepatitis B Virus (HBV); 2.1% had Hepatitis B surface Antigen (HBsAg) and 22.8% had antibody to the Hepatitis B surface Antigen (anti-HBs). The occurrence of HBsAg was higher in ethnic Chinese (6.3%) compared to Malays (1.8%) and Indians (0.9%), even when analyzed by sex, but not with age, type of institution and geographical locality. The distribution of anti-HBs was higher with ethnic Chinese (41.6%), male sex (27.2%) and age. There was a wide variation of the prevalence of serological markers among occupations and increased relative risks of HBsAg were found among medical assistants (RR3.7; 95% CI 1.4-9.1) and laboratory staff (RR 3.2; 95% CI 1-8.8), and that of anti-HBs among medical assistants (RR 2.8; 95% CI 1.8-3.7). The variations of HBsAg among occupations by type of institutions was marginal while that of anti-HBs was higher among attendants and midwives in hospitals, medical assistants in health departments, and assistant nurses and dentists in dental centers. The patterns of distribution of serological markers of HBV among health staff reflect the situation in the community with high endemicity and resemble specific occupational factors noted in previous studies in the West.
Publication year is 1992-1993

Matched MeSH terms: Hepatitis B Surface Antigens/immunology
Antigenicity and immunogenicity of the immunodominant region of hepatitis B surface antigen displayed on bacteriophage T7

Tan GH, Yusoff K, Seow HF, Tan WS

J Med Virol, 2005 Dec;77(4):475-80.
PMID: 16254965

The immunodominant region of hepatitis B virus (HBV) located in the viral small surface antigen (S-HBsAg) elicits virus-neutralizing and protective antibodies. In order to develop an easy and inexpensive method to produce this region without the need for extensive purification, amino acid residues 111-156 of S-HBsAg were fused to the C-terminal end of the 10B capsid protein of T7 phage. Western blotting and ELISA confirmed the expression of the recombinant protein on the surface of the phage particles. The recombinant phage exhibited the antigenic and immunogenic characteristics of HBsAg, illustrating its potential as an immunological reagent and vaccine.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology*
The full-length clone of cucumber green mottle mosaic virus and its application as an expression system for Hepatitis B surface antigen

Ooi A, Tan S, Mohamed R, Rahman NA, Othman RY

J Biotechnol, 2006 Feb 24;121(4):471-81.
PMID: 16271415

A cucumber green mosaic mottle virus (CGMMV) full-length clone was developed for the expression of Hepatitis B surface antigen (HBsAg). The expression of the surface displayed HBsAg by the chimeric virus was confirmed through a double antibody sandwich ELISA. Assessment of the coat protein composition of the chimeric virus particles by SDS-PAGE analysis showed that 50% of the coat proteins were fused to the HBsAg. Biological activity of the expressed HBsAg was assessed through the stimulation of in vitro antibody production by cultured peripheral blood mononuclear cells (PBMC). PBMC that were cultured in the presence of the chimeric virus showed up to an approximately three-fold increase in the level of anti HBsAg immunoglobulin thus suggesting the possible use of this new chimeric virus as an effective Hepatitis B vaccine.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology
Fulltext Immune response in infants after universal hepatitis B vaccination: a community-based study in Malaysia

Cheang HK, Wong HT, Ho SC, Chew KS, Lee WS

Singapore Med J, 2013 Apr;54(4):224-6.
PMID: 23624451

INTRODUCTION: This study aimed to assess the immune response in infants who received the three-shot hepatitis B vaccine in Malaysia.

METHODS: Consecutive infants born between March 2002 and April 2010 who received three doses of hepatitis B vaccine at a community clinic in Malaysia were enrolled in the study. Screening for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) was performed after the completion of primary immunisation, at approximately one year of age.

RESULTS: A total of 572 infants (median age 9.3 ± 2.7 months; range 6.3-48 months) were screened for immune response to hepatitis B vaccination - 553 (96.7%) infants had adequate levels of anti-HBs (≥ 10 IU/L). Of the 440 mothers whose HBsAg status was known, 14 (3.2%) were positive for HBsAg. None of the 14 infants who were born to HBsAg-positive mothers were positive for HBsAg, and all but one infant had anti-HBs level ≥ 10 IU/L. Gender, gestational age and maternal HBsAg status were not found to significantly affect the subsequent immune response in infants following vaccination.

CONCLUSION: The proportion of Malaysian mothers who are positive for HBsAg remains high. The three-shot hepatitis B vaccine, given as part of universal vaccination against hepatitis B, provides adequate anti-HBs in the vast majority of infants in a community setting in Malaysia.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology
Hepatitis B: review of development from the discovery of the "Australia Antigen" to end of the twentieth Century

Yap SF

Malays J Pathol, 2004 Jun;26(1):1-12.
PMID: 16190102

"Parenteral" or "serum" hepatitis is known to have afflicted man for centuries. However, it was not until the mid-1960s that the causative agent of this infection, the hepatitis B virus, was discovered. Since then, the biology and the replication strategy of the virus, and the clinical features and the epidemiology of the hepatitis B infection have been determined. Knowledge about the virus and the infection it causes led to the development of firstly, a plasma-derived vaccine and later a recombinant vaccine for the prevention of the infection. Integration of the hepatitis B vaccine into newborn vaccination programmes on a worldwide basis represents a major step in the effort to eliminate this infectious disease and its complications. Laboratory tests are available for the diagnosis and monitoring of the disease. Therapies have been developed to halt the progress of the chronic infection in affected individuals. While these developments have resulted in a decrease of the frequency of infection in many countries, particularly those that have implemented universal immunization of newborns, the chronic infection remains a significant global problem. Worldwide, over 300 million individuals are infected and each year, an estimated 1 million persons die from chronic complications of the disease including hepatocellular carcinoma and hepatic failure. The therapies currently available result in elimination of the virus in only a relatively small proportion of subjects and carry with it serious side effects. Geopolitical, economic and other factors hinder the vision of elimination of the infection through immunization programmes. Nevertheless, work continues to clarify further the underlying pathological mechanism of the infection, the host and viral factors that promote elimination or persistence of the virus in the human host. It is hoped that such investigations will reveal viral targets for the design of newer and potentially more effective drugs to treat the infection.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology*
Fulltext Naturally occurring hepatitis B virus surface antigen mutant variants in Malaysian blood donors and vaccinees

Hudu SA, Harmal NS, Saeed MI, Alshrari AS, Malik YA, Niazlin MT, et al.

Eur J Clin Microbiol Infect Dis, 2015 Jul;34(7):1349-59.
PMID: 25792010 DOI: 10.1007/s10096-015-2358-1

Hepatitis B virus surface mutants are of enormous importance because they are capable of escaping detection by serology and can infect both vaccinated and unvaccinated populations, thus putting the whole population at risk. This study aimed to detect and characterise hepatitis B-escaped mutants among blood donors and vaccinees. One thousand serum samples were collected for this study from blood donors and vaccinees. Hepatitis B surface antigen, antibodies and core antibodies were tested using a commercial enzyme-linked immunosorbent assay (ELISA) kit. DNA detection was performed via nested polymerase chain reaction (PCR), and the S gene was sequenced and analysed using bioinformatics. Of the 1,000 samples that were screened, 5.5% (55/1,000) were found to be HBsAg-negative and anti-HBc- and HBV DNA-positive. All 55 isolates were found to belong to genotype B. Several mutations were found across all the sequences from synonymous and non-synonymous mutations, with the most nucleotide mutations occurring at position 342, where adenine was replaced by guanine, and cytosine at position 46 was replaced by adenine in 96.4% and 98% of the isolates, respectively. Mutation at position 16 of the amino acid sequence was found to be common to all the Malaysian isolates, with 85.7% of the mutations occurring outside the major hydrophilic region. This study revealed a prevalence of 5.5% for hepatitis B-escaped mutations among blood donors and vaccinated undergraduates, with the most common mutation being found at position 16, where glutamine was substituted with lysine.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology
Fulltext Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response

Ninyio NN, Ho KL, Yong CY, Chee HY, Hamid M, Ong HK, et al.

Int J Mol Sci, 2021 Feb 15;22(4).
PMID: 33672018 DOI: 10.3390/ijms22041922

Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology
Fulltext PreS1 Mutations Alter the Large HBsAg Antigenicity of a Hepatitis B Virus Strain Isolated in Bangladesh

Hossain MG, Mahmud MM, Nazir KHMNH, Ueda K

Int J Mol Sci, 2020 Jan 15;21(2).
PMID: 31952213 DOI: 10.3390/ijms21020546

Mutations in the hepatitis B virus (HBV) genome can potentially lead to vaccination failure, diagnostic escape, and disease progression. However, there are no reports on viral gene expression and large hepatitis B surface antigen (HBsAg) antigenicity alterations due to mutations in HBV isolated from a Bangladeshi population. Here, we sequenced the full genome of the HBV isolated from a clinically infected patient in Bangladesh. The open reading frames (ORFs) (P, S, C, and X) of the isolated HBV strain were successfully amplified and cloned into a mammalian expression vector. The HBV isolate was identified as genotype C (sub-genotype C2), serotype adr, and evolutionarily related to strains isolated in Indonesia, Malaysia, and China. Clinically significant mutations, such as preS1 C2964A, reverse transcriptase domain I91L, and small HBsAg N3S, were identified. The viral P, S, C, and X genes were expressed in HEK-293T and HepG2 cells by transient transfection with a native subcellular distribution pattern analyzed by immunofluorescence assay. Western blotting of large HBsAg using preS1 antibody showed no staining, and preS1 ELISA showed a significant reduction in reactivity due to amino acid mutations. This mutated preS1 sequence has been identified in several Asian countries. To our knowledge, this is the first report investigating changes in large HBsAg antigenicity due to preS1 mutations.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology*
Fulltext Isolated hepatitis B core antibody positive among vaccinated cohort in Malaysia

Hudu SA, Malik YA, Niazlin MT, Harmal NS, Alshrari AS, Sekawi Z

Ann Saudi Med, 2013;33(6):591-4.
PMID: 24413864 DOI: 10.5144/0256-4947.2013.591

BACKGROUND AND OBJECTIVES: Hepatitis B core antibodies (anti-HBc) are detected in almost every patient with previous exposure to hepatitis B virus (HBV). However, with this marker alone, one cannot understand the activity of the disease; therefore, this study aimed to identify the implication of isolated hepatitis B core antibody and evaluate the effect of hepatitis B vaccine booster in isolated anti-HBc among adults who received the HBV vaccine as infants.
DESIGN AND SETTINGS: A prospective cohort study of vaccinated undergraduate students of University Putra Malaysia.
PATIENTS AND METHODS: A total of 408 undergraduate students who received infant hepatitis B vaccination volunteered for this study; 5 mL of venous blood was taken from the volunteers. Hepatitis B surface antigen (HBsAg) and core antibodies were tested using a commercially available enzyme-linked immunosorbent assay kit according to the manufacturer's instructions (DRG international Inc., USA). Molecular detection of hepatitis B viral DNA was performed using nested polymerase chain reaction.
RESULTS: The prevalence of isolated anti-HBc among the vaccinated cohort was found to be 5.0%, out of which 80% had a hepatitis B surface antibodies (anti-HBs) titer higher than 10 IU/L, while 20% had less than 10 IU/L anti-HBs titer. All the anti-HBc positivesubjects had detectable hepatitis B viral DNA in their serum. Anamnestic response was found to be 100% among isolated anti-HBc with negative antibody.
CONCLUSION: Isolated anti-HBc developed protective levels of anti-HBs after a single dose of recombinant hepatitis B vaccination. HBV DNA was detected in all isolated anti-HBc indicating occult chronic HBV infection with undetectable HBsAg.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology*
Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles

Chen XY, Butt AM, Mohd Amin MCI

Mol Pharm, 2019 09 03;16(9):3853-3872.
PMID: 31398038 DOI: 10.1021/acs.molpharmaceut.9b00483

The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology*
Fulltext Evaluation of the dried blood spot (DBS) collection method as a tool for detection of HIV Ag/Ab, HBsAg, anti-HBs and anti-HCV in a Malaysian tertiary referral hospital

Lee CE, Sri Ponnampalavanar S, Syed Omar SF, Mahadeva S, Ong LY, Kamarulzaman A

Ann Acad Med Singap, 2011 Oct;40(10):448-53.
PMID: 22206053 DOI: 10.47102/annals-acadmedsg.V40N10p448

INTRODUCTION: Dried blood spot (DBS) collection is an appealing alternative to whole blood or plasma sampling, as it has technical and economic advantages over the latter.

MATERIALS AND METHODS: A prospective cross-sectional study was conducted at a Malaysian tertiary referral hospital from November 2009 to March 2010. One hundred and fifty paired specimens of DBS and plasma were analysed by the standard assays for HIV Ag/Ab, HBsAg, anti-HBS and anti-HCV, separately (total 600 paired specimens). DBS sample titres were then compared to the results of plasma testing, which was used as the gold standard.

RESULTS: For the HIV Ag/Ab assay with a cut-off point of 0.35 Relative Light Units (RLUs), the sensitivity and specificity were both 100%. For the HBsAg assay, the sensitivity was 96.5% and the specificity was 97.8%, with a cut-off point of 1.72 RLUs. Sensitivity for the anti-HBs test was 74.2% and the specificity was 86.9%, using a cut-off point of 0.635 RLUs. For the anti-HCV assay, the sensitivity was 97.3% and the specificity was 100%, with a cut-off point of 0.10 RLUs.

CONCLUSION: DBS is an ideal choice to be used as a screening tool for the detection of HIV, Hepatitis B and Hepatitis C virus infections. However, different cut-off values need to be used for the validation of test positivity in DBS samples because the small amount of blood in the DBS specimens leads to lower assay titres.

Matched MeSH terms: Hepatitis B Surface Antigens/immunology

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