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1. A review of adjuvants for Leishmania vaccine candidates. J Biomed Res, 2010;
24(1):16-25
Joshua M. Mutisoa, John C. Machariaa, Michael M. Gicherub
a
Department of Tropical and Infectious Diseases, Institute of Primate Research,
National Museums of Kenya,P.O. Box 24481-00502, Karen,Nairobi, Kenya;
b
Department of Zoological Sciences, School of Pure and Applied Sciences, Kenyatta
University,P.O. Box 43844-00100, Nairobi, Kenya.
Abstract: Over the last decade, there has been a flurry of research on adjuvants for
vaccines, and several novel adjuvants are now licensed products or in late stage
clinical development. The success of adjuvants in enhancing the immune response to
antigens has led many researchers to re-focus their vaccine development programs.
Although several vaccine candidates have been tested against leishmaniasis, there is
yet no effective vaccine against this parasitic disease. Recent research has
documented that efforts to develop effective Leishmania vaccine have been limited
due to lack of an appropriate adjuvant. In view of this, this review paper outlines
some of the adjuvants that have been used in Leishmania vaccine candidates and cites
a few of the responses obtained from these studies. The aim of the present review is to
consolidate these findings to facilitate the application of these adjuvants in general
and experimental vaccinology.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100103&flag=1
2. Ultraviolet- attenuated cercariae of Schistosoma japonicum fail to effectively
induce a Th1 response in spite of up-regulating expression of
cytotoxicity-related genes in C57BL/6 mice. J Biomed Res, 2010; 24(4):
277-284
Meijuan Zhanga,b, Fang Tiana, Yanan Gaoa, Minjun Jia,c, Guanling Wua,c
a
Department of Pathogen Biology and Immunology, Nanjing Medical University,
Nanjing, Jiangsu 210029, China;
b
Department of Clinical Laboratory, the first Affliated Hospital of Nanjing
Medical University, Nanjing, Jiangsu 210029, China;
c
Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu
210029, China.
Abstract: Objective: To better understand the reason that Schistosoma japonicum (S.
japonicum) ultraviolet (UV)-radiated cercariae could not induce high level of
protection in C57BL/6 mice. Methods: Microarray technology was performed to
investigate the gene transcription profile in skin draining lymph nodes (sdLNs) at 1 w
after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S. japonicum
in C57BL/6 mice. The expressions of some representative genes were further
confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine
genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from
AC-vaccinated and NC-infected mice were analyzed by real-time PCR at w 3 and 6
post-exposure. Results: The gene expressions of Th1 cytokines, including interferon-γ
(IFN-γ), interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in the sdLNs were
significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the
gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4
and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6
post-vaccination. In addition, cytotoxicity-related molecules including granzyme A,
granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early
stage of vaccination, and peaked at the 3rd w after vaccination with UV-AC.
Conclusion: UV-AC of S. japonicum could not effectively induce a Th1 response in
C57BL/6 mice, which may be an explanation for the low protection against parasite
challenge, and the role played by up-regulated expression of cytotoxicity-related
genes in mice needs to be further investigated.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR100404&flag=1
3. Antigen presenting cells may be able to distinguish between normal and
radiated Schistosoma japonicum cercaria: an in vitro observation. J Biomed
Res, 2010; 24(4):285-291
Guixia Tanga, Minjun Jia,b, Haiwei Wua,b, Guanling Wua,b
a
Department of Pathogen Biology and Immunology, Nanjing Medical University,
Nanjing, Jiangsu 210029, China;
b
Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu
210029, China.
Abstract: Objective: To observe the discrepancies of responses induced by
Schistosoma japonicum (S. japonicum) normal cercaria antigen (NCA) and ultraviolet
(UV) -radiation-attenuated cercaria antigen (UVACA) in an in vitro system. Methods:
S. japonicum cercariae were collected and UVACA and NCA were prepared. Mouse
macro-phage model cells (RAW 264.7) were treated with medium, NCA (40 μg/mL)
or UVACA (40 μg/mL) in the presence or absence of recombinant mouse interferon
gamma (rmIFN-γ; 4 ng/mL) for 48 h. Cell surface staining and flow cytometry were
used to assess the major histocompatibility complex (MHC)Ⅱ expression, and data
were expressed as mean fluorescence intensities (MFI). Interleukin (IL) -10, IL-6 and
prostaglandin E2 (PGE2) in cell culture supernatant were evaluated by commercial
enzyme-linked immunosorbent assays. Results: NCA significantly suppressed
IFN-γ-induced MHCⅡ expression on RAW 264.7 cells. In the presence of IFN-γ,
NCA significantly promoted IL-6, IL-10 and PGE2 secretion from RAW 264.7 cells.
In the presence of IFN-γ, UVACA significantly promoted IL-10 but not IL-6 and
PGE2 secretion from RAW 264.7 cells and showed no effect on IFN-γ-induced MHC
Ⅱ expression. Compared with UVACA, NCA significantly suppressed
IFN-γ-induced MHC Ⅱ expression and significantly promoted IL-6, PGE2 and
IL-10 secretion from RAW 264.7 cells. Conclusion: RAW 264.7 cells respond
differently to NCA and UVACA. NCA can significantly suppress IFN-γ-induced
MHC Ⅱ expression and significantly promote IL-6, IL-10 and PGE2 secretion from
RAW 264.7 cells compared with UVACA.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR100405&flag=1
4. Clostridium difficile infections in China. J Biomed Res, 2010; 24(6):411-416
Ke Jina,b,c, Shixia Wangc,d, Zuhu Huanga,b,c, Shan Lub,c,d
a
Department of Infectious Diseases, bJiangsu Province Key Laboratory in
Infectious Diseases, cChina-US Vaccine Research Center, the First Affiliated
Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;
d
Department of Medicine, University of Massachusetts Medical School, Worcester,
MA 01655, USA.
Abstract: Clostridium difficile (C. difficile) infection has become one of the major
hospital-associated infections in Western countries in the last two decades. However,
there is limited information on the status of C. difficile infection in Chinese healthcare
settings. Given the large and increasing elderly population and the well-recognized
problem of over-prescribing of broad spectrum antibiotics in China, it is critical to
understand the epidemiology and potential risk factors that may contribute to C.
difficile infection in China. A literature review of available published studies,
including those in Chinese language-based journals, was conducted. A review of the
currently available literature suggested the presence of C. difficile infections in China,
but also suggested that these infections were not particularly endemic. This finding
should lead to better designed and greatly expanded studies to provide a more reliable
epidemiologically-based conclusion on the actual status of C. difficile infection in
China, including the identification of any associated risk factors. Such information
is ultimately valuable to develop appropriate strategies to pre-vent C. difficile
infection and the vast negative impact of such infections in China and other
developing countries.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100601&flag=1
5. Human herpesvirus 6A induces apoptosis of HSB-2 cells via a
mitochondrion-related caspase pathway. J Biomed Res, 2010; 24(6):444-451
Lingyun Lia,b, Jing Chia, Feng Zhoua, Dandan Guoa, Fang Wangc, Genyan Liuc, Chun
Zhanga, Kun Yaoa
a
Department of Microbiology and Immunology, Nanjing Medical University,
Nanjing, Jiangsu 210029, China;
bDepartment
c
of Developmental Genetics, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing
Medical University, Nanjing, Jiangsu 210029, China.
Abstract: Apoptosis plays an important role in the pathogenesis of viral infections. In
this study, we investigated the cell death processes during productive HHV-6A
infection and the underlying mechanisms. Annexin V-PI staining and electron
microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A
infection decreased mitochondrial transmembrane potential and led to morphological
changes of mitochondria. The cell death was associated with activation of caspase-3
and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known
to be an important substrate for activated caspase-3. Caspase-9 was activated
significantly in HHV-6A-infected cells, whereas caspase-8 was not activated
obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2.
This is the first demonstration of mitochondrion-mediated, caspase-dependent
apoptosis in HHV-6A-infected cells.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr100605&flag=1
6. Cryptosporidiosis-an overview. J Biomed Res, 2011; 25(1):1-16
Gordon J Leitcha, Qing Heb
a
Department of Physiology, and bDepartment Microbiology, Biochemistry and
Immunology, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
Abstract: Apicomplexan protozoan parasites of the genus Cryptosporidium infect the
gastrointestinal tract and lungs of a wide variety of animals, including humans. The
majority of human infections are due to either Cryptosporidium hominis (C. hominis)
and/or Cryptosporidium parvum (C. parvum). The parasite has a complex life cycle
that includes both asexual and sexual stages. While there are invasive free living
stages, proliferation and differentiation take place within a unique parasitrophorous
vacuole under the host cell brush border but outside the host cell cytoplasm. Infection
is spread by environmentally resistant spores that primarily contaminate drinking
water and occasionally food sources, which may cause significant outbreaks of
diarrhea that generally lasts less than 2 w in immunocompetent individuals. In
immunodeficient or immunosuppressed individuals, diarrhea may be copious and can
result in significant morbidity and mortality, particularly in AIDS patients. Although
diagnosis is relatively simple, effective drug treatment, particulary for infections in
immunodeficient patients, has not been uniformly successful. This overview
summarizes the species known to infect humans, aspects of the parasite life cycle,
sources of infection, the pathophysiology of cryptosporidiosis, the immune response
to infection, diagnosis, treatment and some aspects of cryptosporidiosis in China.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110101&flag=1
7. A survey of HIV infection and related high-risk factors among men who have
sex with men in Suzhou, Jiangsu, China. J Biomed Res, 2011; 25(1):17-24
Hongling Baia, Xiping Huanb, Weiming Tanga, Xin Chena, Hongjing Yanb, Xiaoyan
Liub, Haitao Yangb, Zhihang Penga, Xiuping Zhaoc, Rongbin Yua, Hao Yua, Feng
Chena
a
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing
Medical University, Nanjing, Jiangsu 210029, China;
b
Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu
210009, China;
c
Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu 215004,
China.
Abstract: A cross-sectional study using the snowball sampling method was conducted
in May 2008 to investigate human immunodeficiency virus (HIV) infection status and
related high risk factors among men who have sex with men (MSM) in Suzhou city of
Jiangsu province. The researchers carried out a face-to-face questionnaire interview
among MSM, and collected their blood samples to test for HIV and other sexually
transmitted diseases (STDs). Among the 280 respondents, 91.1% had homosexual
acts in the past 6 months and 87.5% had multiple homosexual partners; 46.4% had
heterosexual sex in the past 6 months and 33.1% had multiple heterosexual partners.
The rate of continued condom use was 44.3% in homosexual sex in the past 6 months,
while the rate in heterosexual sex was 33.9%. Laboratory test results showed that the
prevalences of HIV and syphilis were 7.1% (20/280) and 15.0% (42/280),
respectively, but no HCV-positive person was found. In the multivariate logistic
regression mod-el, subjects with a monthly income of more than RMB ¥ 1,000
(OR=4.83,95% CI=1.44-16.22), subjects who often went to bars for sexual partners
(OR=2.25, 95%CI=1.21-4.20), and subjects who had more than one sexual partner in
the past 6 months (OR=0.49, 95%CI=0.25-0.97) and had sex with fixed sexual
partners in the past 6 months (OR=0.42, 95%CI=0.25-0.75) were significantly
associated with the rate of continued condom use in homosexual sex in the past 6
months. Unprotected sex and multiple sexual partners were more common among
MSM in Suzhou city; furthermore, the prevalences of HIV infection and syphilis were
relatively high. HIV preventive measures should be designed to address these risk
factors and control the spread of HIV among MSM.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110102&flag=1
8. A functional type I interferon pathway drives resistance to cornea herpes
simplex virus type 1 infection by recruitment of leukocytes. J Biomed Res,
2011; 25(2):111-119
Christopher D. Conradya, Heather Jonesa, Min Zhengb, Daniel J.J. Carra,b
a
Departments of Microbiology, Immunology, and bOphthalmology, The University
of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
Abstract: Type I interferons are critical antiviral cytokines produced following herpes
simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present
study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the
source of interferon-α. We also report mice deficient in the A1 chain of the type I IFN
receptor (CD118-/-) are extremely sensitive to ocular infection with low doses (100
PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea compared to
wild type (WT) controls. The enhanced susceptibility correlated with a loss of CD4+
and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite
mounting an adaptive immune response in the draining mandibular lymph node of
CD118-/- mice. Taken together, these results highlight the importance of IFN
production in both the innate immune response as well as eliciting chemokine
production required to facilitate adaptive immune cell trafficking.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110204&flag=1
9. Identification of distant co-evolving residues in antigen 85C from
Mycobacterium tuberculosis using statistical coupling analysis of the esterase
family proteins. J Biomed Res, 2011; 25(3):165-169
Veeky Baths, Utpal Roy
Department of Biological Sciences, BITS Pilani K. K Birla Goa Campus, GOA
403726, India.
Abstract: A fundamental goal in cellular signaling is to understand allosteric
communication, the process by which signals originating at one site in a protein
propagate reliably to affect distant functional sites. The general principles of protein
structure that underlie this process remain unknown. Statistical coupling analysis
(SCA) is a statistical technique that uses evolutionary data of a protein family to
measure correlation between distant functional sites and suggests allosteric
communication. In proteins, very distant and small interactions between collections of
amino acids provide the communication which can be important for signaling process.
In this paper, we present the SCA of protein alignment of the esterase family (pfam
ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium
tuberculosis to identify a subset of interacting residues. Clustering analysis of the
pairwise correlation highlighted seven important residue positions in the esterase
family alignments. These residues were then mapped on the crystal structure of
antigen 85C (PDB ID: 1DQZ). The mapping revealed correlation between 3 distant
residues (Asp38, Leu123 and Met125) and suggests allosteric communication
between them. This information can be used for a new drug against this fatal disease.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110302&flag=1
10. Role of remote sensing, geographic bioinformatics system and bioinformatics
in kala-azar epidemiology. J Biomed Res, 2011; 25(6):373-384
Gouri Sankar Bhunia, Manas Ranjan Dikhit, Shreekant Kesari, Ganesh Chandra
Sahoo, Pradeep Das
Rajendra Memorial Research Institute of Medical Sciences (ICMR), Agamkuan,
Patna, Bihar 800007, India.
Abstract: Visceral leishmaniasis or kala-azar is a potent parasitic infection causing
death of thousands of people each year. Medicinal compounds currently available for
the treatment of kala-azar have serious side effects and de-creased efficacy owing to
the emergence of resistant strains. The type of immune reaction is also to be
considered in patients infected with Leishmania donovani (L. donovani). For
complete eradication of this disease, a high level modern research is currently being
applied both at the molecular level as well as at the field level. The computational
approaches like remote sensing, geographic information system (GIS) and
bioinformatics are the key re-sources for the detection and distribution of vectors,
patterns, ecological and environmental factors and genomic and proteomic analysis.
Novel approaches like GIS and bioinformatics have been more appropriately utilized
in determining the cause of visearal leishmaniasis and in designing strategies for
preventing the disease from spreading from one region to another.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR110601&flag=1
11. Leishmania donovani whole cell antigen delivered with adjuvants protects
against visceral leishmaniasis in vervet monkeys (Chlorocebus aethiops) . J
Biomed Res, 2012; 26(1):8-16
Joshua Muli Mutisoa,b, John Chege Machariaa, Evans Tarachaa, Michael Muita
Gicherub
a
Department of Tropical and Infectious Diseases, Institute of Primate Research,
Karen, Nairobi 24481-00502, Kenya;
b
Department of Zoological Sciences, Kenyatta University, Nairobi 43844-00100,
Kenya.
Abstract: In a previous immunogenicity and efficacy study in mice, montanide ISA
720 (MISA) was indicated to be a better adjuvant than bacillus calmette guerin
vaccine (BCG) for a Leishmania vaccine. In the present study, we report the safety,
immunogenicity and efficacy of Leishmania donovani (L. donovani) sonicated
antigen delivered with alum-BCG (AlBCG), MISA or monophosphoryl lipid A
(MPLA) in vervet monkeys following intradermal inoculums. Vaccinated and control
animals were challenged with virulent L. donovani parasites and the parasitic burden
was determined. Only animals vaccinated with alum-BCG adversely reacted to the
inoculum by producing ulcerative erythematous skin indurations. Non-parametric
ANOVA followed by a post test showed significantly higher IgG antibodies, and
revealed the presence of lymphoproliferative and interferon gamma responses in both
AlBCG+Ag and MISA+Ag as compared to the MPLA+Ag or other groups (P <
0.001). We conclude that L. donovani sonicated antigen containing MISA is safe and
is associated with protective immune response against Leishmania donovani infection
in the vervet monkey model.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120102&flag=1
12. Prevalence of intestinal parasitic infections in certified food-handlers
working in food establishments in the City of Nairobi, Kenya. J Biomed Res,
2012; 26(2):84-89
Paul Kamaua, c, Penina Aloo-Obudhoa, Ephantus Kabirub, Kepha Ombachoc, Bernard
Langatd, Obadiah Mucherue, Laban Irerie
a
Department of Zoological Sciences, Kenyatta University, Nairobi, Kenya;
b
Department of Pathology, Kenyatta University, Nairobi, Kenya;
c
Ministry of Public Health and Sanitation, Nairobi, Kenya;
d
Institute of Tropical Medicine and Infectious Diseases, Jomo Kenyatta University
of Agriculture and Technology, Nairobi, Kenya;
e
Division of Vector Borne and Neglected Tropical Diseases, Embu, Kenya.
Abstract: Most intestinal parasites are cosmopolitan with the highest prevalence in the
tropics and subtopics. Rural-to-urban migration rapidly increases the number of food
eating places in towns and their environs. Some of these eating estabishments have
poor sanitation and are overcrowded, facilitating disease transmission, especially
through food-handling. Our investigations in Nairobi, therefore, were set to determine
the presence of intestinal parasites in food-handlers with valid medical certificates.
Direct and concentrated stool processing techniques were used. Chi-square test and
ANOVA were used for data analysis. The parasites Ascaris lumbricoides, Entamoeba
histolytica and Giardia lamblia were observed in certified food-handlers. Significant
difference was found in parasite frequency by eating classes and gender (χ2 = 9.49, P
= 0.73), (F = 1.495, P = 0.297), but not in parasite occurrence between age brackets
(χ2 = 6.99, P = 0.039). The six-month medical certificate validity period may
contribute significantly to the presence of intestinal parasites in certified
food-handlers.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120203&flag=1