Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1) is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated) and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1) was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1) was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA) and rROP1 from pVAX1-ROP1 and rROP1-immunized mice, respectively, readily proliferated and secreted large amount of IFN-γ (712 ± 28.1 pg/ml and 1457 ± 31.19 pg/ml, respectively) and relatively low IL-4 level (94 ± 14.5 pg/ml and 186 ± 14.17 pg/ml, respectively). These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis.
Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.
A Newcastle disease virus (NDV) isolate designated IBS002 was isolated from a commercial broiler farm in Malaysia. The virus was characterised as a virulent strain based on the multiple basic amino acid motif of the fusion (F) cleavage site (112)RRRKGF(117) and length of the C-terminus extension of the hemagglutinin-neuraminidase (HN) gene. Furthermore, IBS002 was classified as a velogenic NDV with mean death time (MDT) of 51.2 h and intracerebral pathogenicity index (ICPI) of 1.76. A genetic distance analysis based on the full-length F and HN genes showed that both velogenic viruses used in this study, genotype VII NDV isolate IBS002 and genotype VIII NDV isolate AF2240-I, had high genetic variations with genotype II LaSota vaccine. In this study, the protection efficacy of the recombinant genotype VII NDV inactivated vaccine was also evaluated when added to an existing commercial vaccination program against challenge with velogenic NDV IBS002 and NDV AF2240-I in commercial broilers. The results indicated that both LaSota and recombinant genotype VII vaccines offered full protection against challenge with AF2240-I. However, the LaSota vaccine only conferred partial protection against IBS002. In addition, significantly reduced viral shedding was observed in the recombinant genotype VII-vaccinated chickens compared to LaSota-vaccinated chickens.
METHODS: Healthy women aged 18-35 years received intramuscularly three doses of either the vaccine (HPV group) or aluminium hydroxide (ALU group) at 0, 1, and 6 months. Antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA).
RESULTS: A total of 271 eligible subjects were enrolled and 266 subjects completed the study. Initially seronegative subjects in the HPV group showed 100% seroconversion one month post-dose-3 for anti HPV-16 and anti-HPV-18 antibodies with geometric mean titers of 11107.5 (95% CI: 9727.3-12683.4) EL.U/mL and 4273.5 (95% CI: 3771.8-4841.9) EL.U/mL, respectively. Over 96% of subjects in both groups received all three vaccine doses. Solicited local (pain) and general symptoms (myalgia, fatigue, arthralgia and headache) were commonly reported in both HPV and ALU groups. Eight serious adverse events were reported throughout the study (five in the HPV group; three in the ALU group), all considered by investigators to be unrelated to vaccination.
CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was immunogenic and generally well tolerated in Malaysian women aged 18-35 years.
Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.
Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now.
Human papillomavirus has been established as the causal agent for cervical cancer. The identification of a clear cause presents an unparalleled opportunity for cancer control. As such, the development of prophylactic human papillomavirus vaccines has been rightly hailed as one of the significant scientific triumphs of the past 20 years. This story of scientific triumph over disease, however, is not yet complete. The fruit of scientific labour must be delivered to the people in order to fulfil the underlying intent of the research (i.e. to prevent cancer and save lives). The success of a vaccination programme, however, does not depend on the biological efficacy of the vaccine alone. Various other local factors, such as poverty, gender inequality, cultural traditions, or religious beliefs, can significantly constrain the success of any vaccination programme. In this chapter, we provide an overview of how the human papillomavirus vaccine works and its global uptake, as well as, how variations in local contexts can affect the successful implementation of a vaccination programme. Other factors besides vaccine costs also need serious attention. With better understanding of such factors, policy makers and medical health professionals will be better equipped to make informed decisions to maximise the potential benefits of the human papillomavirus vaccines for the most number of people in individual countries.
Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination.
Chronic wounds and scar tissues are prone to skin cancer. In 1828, Jean-Nicholas Marjolin described the occurrence of tumours in post-traumatic scar tissue. He did not, however, identify the warty ulcers he described as malignant. It was Dupuytren, who about two years later, noted that these lesions were cancerous. The eponym was bestowed by Da Costa in 1903. Marjolin's ulcer no longer refers only to carcinomas secondary to burns and is classified as a malignancy that arises from previously traumatised, chronically inflamed, or scarred skin. It has been reported in relation to osteomyelitis, venous stasis ulcer, tropical ulcers, chronic decubitus ulcer, frostbite, pilonidal sinus, vaccination site, urinary fistula, hidradenitis suppurativa, skin graft donor site, gunshot wounds, puncture wounds, dog bites, and lupus rash. Early arising Marjolin's ulcer has rarely been described in literature. In this case report, we present the CT appearances of Marjolin's ulcer in the left gluteal region of a young man.
Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.
The present study describes the development of DNA vaccines using the hemagglutinin-neuraminidase (HN) and fusion (F) genes from AF2240 Newcastle disease virus strain, namely pIRES/HN, pIRES/F and pIRES-F/HN. Transient expression analysis of the constructs in Vero cells revealed the successful expression of gene inserts in vitro. Moreover, in vivo experiments showed that single vaccination with the constructed plasmid DNA (pDNA) followed by a boost with inactivated vaccine induced a significant difference in enzyme-linked immunosorbent assay antibody levels (p < 0.05) elicited by either pIRES/F, pIRES/F+ pIRES/HN or pIRES-F/HN at one week after the booster in specific pathogen free chickens when compared with the inactivated vaccine alone. Taken together, these results indicated that recombinant pDNA could be used to increase the efficacy of the inactivated vaccine immunization procedure.
A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71.
This retrospective study documents a strong correlation between tuberculin reactivity and the subsequent development of active tuberculosis in student nurses. 12% of the 25 student nurses with tuberculin reactions above 20 mm developed tuberculosis over a period of 2 years, compared to only 0.3% of the 341 student nurses with reactions of 20 mm or less. The implications of these findings for preventive therapy are discussed.
Poliomyelitis in Malaysia has not been reported since 1986. We report two cases of poliomyelitis in non-immunized children whose parents, though relatively educated, opted not to vaccinate their children for socio-cultural reasons. This recent trend may interfere with our attempts to eradicate poliomyelitis globally by the year 2000. The clinical features, pathophysiology and differential diagnosis are discussed.
Introduction: Universal HBV and HCV screening among pregnant women is not a current practice in Malaysia. It is aimed to conduct a systematic review on available evidences in an effort to strengthen the national hepatitis screen-ing programs. Methods: Systematic search was performed from databases; Medline, Cochrane, PubMed and IN-AHTA. Relevant studies according to inclusion/exclusion criteria were critically appraised and evidence graded. Re-sults: From 782 titles identified, two systematic reviews, two retrospective cohort studies, two cross-sectional studies, one cost-utility analysis and one cost-effectiveness analysis were included. Universal antenatal HBV screening was associated with almost complete vaccination coverage for newborns. Replacing targeted screening with universal HBV screening was associated with increased identification of newborns indicated for HBV-immunization from 50% to 96%. Universal antenatal HBV screening had incremental cost-effectiveness ratio (ICER)s ranged from €2,032 to €26,181 per life year (LY) gained. As for HCV, targeted antenatal screening was associated with low HCV prevalence. Universal screening did not detect significantly more women with HCV infection than did targeted screening. One cost-effectiveness analysis found that universal antenatal HCV screening had ICER of €52,473 per LY gained and one cost-utility analysis reported ICER of £9,139 per QALY gained. Conclusion: Based on the above review, universal HBV screening in pregnant women is effective in increasing vaccination coverage for newborns. However, the ICERs had wide range. Therefore, local economic evaluation is needed to estimate cost implications before considering addition into national screening program. While for HCV, both universal and targeted screening in pregnant women had low detection rate thus high-risk approach screening is appropriate in Malaysia.
Caseous lymphadenitis (CLA) caused by Corynebacterium pseudotuberculosis is characterized by the development of abscesses, mainly in superficial and internal lymph nodes, visceral and reproductive organs in small ruminants. This study aims to examine the histopathological changes in reproductive organs of goats immunized with killed vaccine of C. pseudotuberculosis. In this study, twenty four (24) clinically healthy bucks and does were divided into four groups A, B, C and D. Animals in groups A and B were immunized with 0.5 and 1% formalin killed vaccine, respectively; followed by a booster dose. After the booster dose of immunization, groups A, B and C were challenged with C. pseudotuberculosis at 106 cfu/ml. Goats in group D were immunize and unchallenged and left as control group. All C. pseudotuberculosis infected animals were euthanized humanely 12 weeks post-challenged. Tissue samples such as testes, epididymis, spermatic cord, penis, pituitary gland, mammary gland, vulva, vagina, cervix, uterus, fallopian tube and ovaries were collected for histopathology study. Microscopic examination of all tissues (testes, seminiferous tubules, spermatic cord, penile tissues and the pituitary gland) in the male reproductive organs of the bucks that were inoculated with 2 ml of 0.5% and 1.0% of C. pseudotuberculosis killed vaccine showed normal (animals inoculated with 1.0%) to mild (animals inoculated with 0.5%) histopathological changes when compared with those from group C which showed varying degrees of histopathological changes (p