Current status of vaccine research, development, and challenges of vaccines for  Mycoplasma gallisepticum

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Abstract

Mycoplasma gallisepticum ( MG) is an important avian pathogen that causes significant economic losses in the poultry industry. Surprisingly, the limited protection and adverse reactions caused by the vaccines, including live vaccines, bacterin-based (killed) vaccines, and recombinant viral vaccines is still a major concern. Mycoplasma gallisepticum strains vary in infectivity and virulence and infection may sometimes unapparent and goes undetected. Although extensive research has been carried out on the biology of this pathogen, information is lacking about the type of immune response that confers protection and selection of appropriate protective antigens and adjuvants. Regardless of numerous efforts focused on the development of safe and effective vaccine for the control of MG, the use of modern DNA vaccine technology selected in silico approaches for the use of conserved recombinant proteins may be a better choice for the preparation of novel effective vaccines. More research is needed to characterize and elucidate MG products modulating MG-host interactions. These products could be used as a reference for the preparation and development of vaccines to control MG infections in poultry flocks.

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Most cited references 123

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Molecular biology and pathogenicity of mycoplasmas.

S RAZIN, D Yogev, Y. Naot (1998)

The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors' chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.

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Immune responses to AAV vectors: overcoming barriers to successful gene therapy.

Federico Mingozzi, Katherine High (2013)

Gene therapy products for the treatment of genetic diseases are currently in clinical trials, and one of these, an adeno-associated viral (AAV) product, has recently been licensed. AAV vectors have achieved positive results in a number of clinical and preclinical settings, including hematologic disorders such as the hemophilias, Gaucher disease, hemochromatosis, and the porphyrias. Because AAV vectors are administered directly to the patient, the likelihood of a host immune response is high, as shown by human studies. Preexisting and/or recall responses to the wild-type virus from which the vector is engineered, or to the transgene product itself, can interfere with therapeutic efficacy if not identified and managed optimally. Small-scale clinical studies have enabled investigators to dissect the immune responses to the AAV vector capsid and to the transgene product, and to develop strategies to manage these responses to achieve long-term expression of the therapeutic gene. However, a comprehensive understanding of the determinants of immunogenicity of AAV vectors, and of potential associated toxicities, is still lacking. Careful immunosurveillance conducted as part of ongoing clinical studies will provide the basis for understanding the intricacies of the immune response in AAV-mediated gene transfer, facilitating safe and effective therapies for genetic diseases.

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Density-dependent decline of host abundance resulting from a new infectious disease.

W. M. Hochachka, A A Dhondt (2000)

Although many new diseases have emerged within the past 2 decades [Cohen, M. L. (1998) Brit. Med. Bull. 54, 523-532], attributing low numbers of animal hosts to the existence of even a new pathogen is problematic. This is because very rarely does one have data on host abundance before and after the epizootic as well as detailed descriptions of pathogen prevalence [Dobson, A. P. & Hudson, P. J. (1985) in Ecology of Infectious Diseases in Natural Populations, eds. Grenfell, B. T. & Dobson, A. P. (Cambridge Univ. Press, Cambridge, U.K.), pp. 52-89]. Month by month we tracked the spread of the epizootic of an apparently novel strain of a widespread poultry pathogen, Mycoplasma gallisepticum, through a previously unknown host, the house finch, whose abundance has been monitored over past decades. Here we are able to demonstrate a causal relationship between high disease prevalence and declining house finch abundance throughout the eastern half of North America because the epizootic reached different parts of the house finch range at different times. Three years after the epizootic arrived, house finch abundance stabilized at similar levels, although house finch abundance had been high and stable in some areas but low and rapidly increasing in others. This result, not previously documented in wild populations, is as expected from theory if transmission of the disease was density dependent.

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Author and article information

Contributors

Wenxin Guo

Jichang Li

Journal

Journal ID (nlm-ta): Poult Sci

Journal ID (iso-abbrev): Poult Sci

Title: Poultry Science

Publisher: Elsevier

ISSN (Print): 0032-5791

ISSN (Electronic): 1525-3171

Publication date PMC-release: 27 June 2020

Publication date Collection: September 2020

Publication date (Electronic): 27 June 2020

Volume: 99

Issue: 9

Pages: 4195-4202

Affiliations

[∗ ]Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China

[† ]Department of Animal Health, The University of Agriculture Peshawar, Khyber Pakhtunkhwa 25130, Pakistan

[‡ ]Department of Veterinary Drug Residues, Heilongjiang Province Agricultural Products And Veterinary Medicine Feed Technology, Appraisal Station 150030

Author notes

[1 ]Corresponding authors: 1018633122@ 123456qq.com lijichang828@ 123456sina.com

Article

Publisher Item ID: S0032-5791(20)30376-X

DOI: 10.1016/j.psj.2020.06.014

PMC ID: 7598112

PubMed ID: 32867963

SO-VID: eb22bfb6-7018-4c55-9909-c181cb2db2b3

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Current status of vaccine research, development, and challenges of vaccines for Mycoplasma gallisepticum

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Abstract

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Vaccines

Most cited references 123

Molecular biology and pathogenicity of mycoplasmas.

Immune responses to AAV vectors: overcoming barriers to successful gene therapy.

Density-dependent decline of host abundance resulting from a new infectious disease.

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