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Microbiology Independent Research Journal (MIR Journal)

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Vol 3, No 1 (2016)
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1-12 230
Abstract

Periodically emerging new influenza strains along with the lack of population immunity to these new viruses can lead to a pandemic, making influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is one of the reasons for the existing influenza virus antigenic diversity in nature and the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, however, the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity developed after disease or immunization poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting wide cross-protective immunity, and is able to resist to influenza A and B viruses of all known subtypes. Basic approaches and challenges in creating such a vaccine are discussed in this review.

13-24 156
Abstract

The biological basis for the restricted immunogenicity of some live attenuated influenza vaccine strains generated on the backbone of the cold adapted (ca) A/Singapore/1/1957/ca (H2N2) influenza A virus master strain and produced in the Vero cells was investigated. According to our previous results the vaccine candidate made from A/Hong Kong/1035/1998 (H1N1) Vero-derived virus did not provoke a measurable antibody titers following the intranasal immunization of humans. We report here that the hemagglutinin (HA) of A/Hong Kong/1035/1998 virus contained the mutation 10Ile→Val in the HA2 subunit, that increased the pH threshold of HA conformational change (pH of activation) by 0.3 pH units and therefore might be responsible for the lack of immune response in humans. Similar effect was shown for the reassortant made from the Vero-derived A/Switzerland/5389/1995 (H1N1) (5389wt) virus which had the HA2 mutation 3Phe→Leu leading to the lack of immune response in mice. Another factor compromising the immunogenicity of a vaccine candidate is the incompatibility of epidemic virus HA with the M gene of the master strain. In mice the 6/2 A/Switzerland/5389/1995 reassortant induced antibodies that were directed predominantly to the HA2 subunit and were detectable by ELISA but not by a hemagglutination inhibition (HAI) test. In contrast, the 5/3 reassortant, bearing the HA, neuraminidase (NA), and M genes from the epidemic virus induced an equivalent amount of antibodies against the HA1 and HA2 subunits detected by HAI and ELISA. By comparing the sensitivity of the viruses to amantadine, we showed that the M2 ion channel of the master strain had lower activity than that of the A/Switzerland/5389/1995. These data suggest that M2 of the master strain was not sufficiently active to keep the pH of the transGolgi network high enough to prevent the conformational change of the acid sensitive HA to the low pH form.
Overall, the adaptation mutations in the HA of the vaccine candidate that increase the pH of HA activation as well as the incompatibility of HA and M genes must be taken into consideration when constructing the reassortant strains for the live attenuated vaccine.

25-30 181
Abstract

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. Type of the bond between sialic acid (SA) and neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. The Yamagata-like virus strains are predominantly bound to α2,6-sialylated glycans, while Victoria-like strains are bound to both α2,3- and α2,6-sialylated glycans. However, the receptor-binding specificity of influenza B viruses has not been characterized enough. In this study, we selected escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). Analysis of the amino acid sequences of mAb-induced escape-mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.

31-41 529
Abstract

The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review.

42-48 184
Abstract

The cold-adapted reassortant influenza virus А/17/herring gull/Sarma/2006/887 (H6N1) was developed in chicken embryos by genetic reassortment based on the A/Leningrad/134/17/57 (H2N2) master donor virus. The genome composition of the obtained reassortant was analyzed by means of real time PCR with the high resolution melting (HRM-analysis) using an intercalating fluorescent dye EvaGreen. Analysis of the DNA copies melting curves of RNA gene fragments (PB2, PB1, PA, NP, M, NS) showed that the reassortant influenza virus А/17/herring gull/2006/887(H6N1) contained the internal proteins coding genes from the master donor virus and the surface antigens coding genes from the A/herring gull/Sarma/51c/2006 (H6N1) avian influenza virus. The study of phenotypic properties showed that the А/17/herring gull/Sarma/2006/887 (H6N1) is temperature sensitive (ts) and coldadapted (ca) in chicken embryos and attenuated in mice when administered intranasally. This reassortant can be recommended as a live influenza vaccine candidate for humans.

49-55 201
Abstract

An analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of developed equine vaccine include: long lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus in 12 months after a double vaccination and the differentiation of infected animals from vaccinated animals.

56-60 159
Abstract

Influenza A and B viruses use sialylated oligosaccharide chains expressed on the surface of a host cell as the cell entry receptors. The type of the bond between sialic acid (SA) and the neighboring galactose residue (Gal) is one of the main characteristics that define the type of receptor. Influenza viruses recognize SAα2-3Gal- or SAα2-6Gal-structures on the surface of the cells. Influenza A viruses of avian origin bind α2-3-sialylated glycans, while the human strains bind preferentially α2-6-sialylated ones. However, the receptor-binding specificity of influenza B viruses has not been characterized sufficiently so far. In this study, we selected the escape mutants of influenza B/Florida/04/2006 strain (Yamagata-like lineage) using monoclonal antibodies (mAb) to hemagglutinin (HA). The analysis of the amino acid sequences of mAb-induced escape mutants revealed the single amino acid substitutions 40Tyr→His, 85His→Tyr, 202Asn→Lys and 242Ser→Arg in 10F4-, 8Н11-, 8Н3- and 9А3-induced HA variants, correspondingly. It was shown that the single amino acid substitutions 202Asn→Lys and 242Ser→Arg alter the receptor-binding specificity of the influenza B virus. These findings are important for the understanding of the influence of individual amino acid residues in HA on the receptor-binding properties of influenza B Yamagata-like lineage viruses and allow us to predict the possible ways of their evolution.

61-67 156
Abstract

The avian influenza viruses of H6N1subtype present a potential danger for humans. The cold-adapted (ca) reassortant influenza virus А/17/herring gull/Sarma/2006/887 (H6N1) was obtained in chicken embryos by the genetic reassortment based on the coldadapted A/Leningrad/134/17/57 (H2N2) master strain. The genome composition of the obtained reassortant was analyzed by means of real-time PCR with the high resolution melting (HRM) analysis using the intercalating fluorescent dye EvaGreen. Analysis of the gene segments showed that the reassortant А/17/herring gull/Sarma/2006/887 (H6N1) contains the internal proteins coding genes (PB2, PB1, PA, NP, M, and NS) of the master donor virus and the surface antigens coding genes of the A/herring gull/Sarma/51c/2006 (H6N1) avian influenza virus. The study of the phenotypic properties showed that the virus А/17/herring gull/Sarma/2006/887 (H6N1) is temperature sensitive (ts), ca in chicken embryos, and attenuated in mice when administered intranasally. This reassortant can be recommended as a live influenza vaccine candidate for humans.

68-73 180
Abstract

An analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses (EIVs) is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted (ca) equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of the developed equine vaccine include: long-lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus at 12 months after double vaccination and the differentiation of infected from vaccinated animals.



ISSN 2500-2236 (Online)