Glanders being a potentially fatal infection has continued to re emerge at various locations in India sporadically. What is the latest in early diagnosis and vaccine development against Glanders.
The killed glanders whole-cell adsorbed vaccine (KGCAV) is available in Russia for immunisation against glanders since 2006. This is a typical killed whole-cell vaccine that consists of a suspension of bacteria of the wild-type but avirulent Burkholderia mallei strain 11 inactivated with formaldehyde, and supplemented with aluminum hydroxide as an adjuvant. A single s.c. injection of the vaccine elicited a pronounced titer of specific antibodies in sera of 46.3%, 53.6% and 27.3% of individuals at one, six, and twelve months post-vaccination, respectively. See:
Russian vaccines against especially dangerous bacterial pathogens
Valentina A Feodorova et al., Emerging Microb Infection 2014
See:
2. Protection of non-human primates against glanders with a goldnanoparticle glycoconjugate vaccine. Alfredo G. Torres et al., 2015.
(1)Battelle, 505 King Ave, Columbus, OH 43201-2693, USA. [email protected].
Glanders is a highly contagious and often fatal zoonotic disease, primarily of
solipds. In the developed world, glanders has been eradicated. However, prior use of B. mallei as a biological weapon and its high mortality in inhalation animal
studies has affirmed B. mallei as a biodefense concern. This threat requires the
development of new glanders medical countermeasures (MCMs), as there is a lack of an effective vaccine and lengthy courses of multiple antibiotics needed to
eradicate B. mallei. Here, we present a literature review of human glanders in
which we discuss the clinical epidemiology and risk factors, potential routes of
exposure, symptoms, the incubation period, and specific diagnostics. This review
focuses on pulmonary glanders, as this is the most likely outcome of a biological
weapons attack. Additionally, we outline current treatment regimens and propose a clinical definition of human pulmonary glanders infection.
2. Front Cell Infect Microbiol. 2013 Feb 5;3:5. doi: 10.3389/fcimb.2013.00005.
eCollection 2013.
Burkholderia vaccines: are we moving forward?
Choh LC(1), Ong GH, Vellasamy KM, Kalaiselvam K, Kang WT, Al-Maleki AR, Mariappan
V, Vadivelu J.
The genus Burkholderia consists of diverse species which includes both "friends"
and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the
biotechnological and agricultural industry for bioremediation and biocontrol.
However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B.
pseudomallei and B. mallei are the causative agents of melioidosis and glanders,
respectively, while B. cepacia infection is lethal to cystic fibrosis (CF)
patients. Due to the high rate of infectivity and intrinsic resistance to many
commonly used antibiotics, together with high mortality rate, B. mallei and B.
pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for
Burkholderia vaccines. Although the search for a prophylactic therapy candidate
continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on
development of safe vaccines with high efficacy against B. pseudomallei, B.
mallei, and B. cepacia. It can be concluded that further research will enable
elucidation of the potential benefits and risks of Burkholderia vaccines.
3. Front Cell Infect Microbiol. 2013 Mar 11;3:10. doi: 10.3389/fcimb.2013.00010.
eCollection 2013.
Development of Burkholderia mallei and pseudomallei vaccines.
Silva EB(1), Dow SW.
Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may
develop after recovery from acute infection with both agents, and control of
infection with antibiotics requires prolonged treatment. Symptoms for both
meliodosis and glanders are non-specific, making diagnosis difficult. B.
pseudomallei can be located in the environment, but in the host, B. mallei and B.
psedomallei are intracellular organisms, and infection results in similar immune
responses to both agents. Effective early innate immune responses are critical to
controlling the early phase of the infection. Innate immune signaling molecules
such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In
contrast, the role of adaptive immune responses in controlling Burkholderia
infection is less well understood. However, T cell responses are critical for
vaccine protection from Burkholderia infection. At present, effective vaccines
for prevention of glanders or meliodosis have not been developed, although
recently development of Burkholderia vaccines has received renewed attention.
This review will summarize current and past approaches to develop B. mallei and
B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated
bacteria provides the most effective and durable immunity, and it is important
therefore to understand the immune correlates of protection induced by live
attenuated vaccines. Subunit vaccines have typically provided less robust
immunity, but are safer to administer to a wider variety of people, including
immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection.
In response to the epidemiological situation, live attenuated or killed vaccines
against anthrax, brucellosis, cholera, glanders, plague and tularemia were
developed and used for immunization of at-risk populations in the Former Soviet
Union. Certain of these vaccines have been updated and currently they are used on a selective basis, mainly for high risk occupations, in the Russian Federation.
Except for anthrax and cholera these vaccines currently are the only licensed
products available for protection against the most dangerous bacterial pathogens.
Development of improved formulations and new products is ongoing.
PMID: 26038506 [PubMed]
5. Curr Med Chem. 2015;22(14):1719-33.
Exploiting molecular virulence determinants in burkholderia to develop vaccine
antigens.
Casey WT, McClean S(1).
The Burkholderia genus is a highly diverse group of species that are distributed
throughout a wide range of environments and habitats. Among this group, which is remarkable for its adaptability to a wider range of environmental conditions
including disinfectants and organic solvents, are a subgroup that represents some of the most difficult to treat infections. This subgroup includes Burkholderia
pseudomallei, the causative agent of melioidosis; B. mallei, the causative agent
of glanders and B. cepacia complex (Bcc) which causes opportunistic infections in people with cystic fibrosis and immunocompromised patients. The latter pathogen is itself a group of 18 distinct, but, closely related species. The adaptability of this group allows the expression of a rich selection of molecular virulence determinants to facilitate its survival in the diverse habitats that it
colonises. This review will describe a selection of these associated with human
infection; comparing them across the three pathogens and highlighting their
potential roles as vaccine candidates. Better integration of the knowledge on the
pathogenesis and molecular determinants of virulence for these Burkholderia spp
may allow the development of more efficacious vaccines.