Giuseppe
Emeritus
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(1.2): J Immunol. 2008 Feb 1;180(3):1758-68.
Healthy Human Subjects Have CD4+ T Cells Directed against H5N1 Influenza Virus.
Roti M, Yang J, Berger D, Huston L, James EA, Kwok WW.
Benaroya Research Institute at Virginia Mason.
It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus.
In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection.
Adults born before 1968 have likely been exposed to H2N2 viruses.
We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes.
Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses.
Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus.
These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain.
However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved.
Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes.
H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13.
These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
PMID: 18209073 [PubMed - in process]
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(1.5): J Virol. 2008 Jan 23 [Epub ahead of print]
Identification of the progenitors of Indonesia and Vietnam avian influenza A (H5N1) viruses from southern China.
Wang J, Vijaykrishna D, Duan L, Bahl J, Zhang JX, Webster RG, Peiris JS, Chen H, Smith GJ, Guan Y.
International Institute of Infection and Immunity, Shantou University, Shantou, Guangdong 515031, China; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38015, USA.
The transmission of highly pathogenic avian influenza (HPAI) H5N1 virus to Southeast Asian countries triggered the first major outbreak and transmission wave in late 2003, accelerating the pandemic threat to the world.
Due to the lack of influenza surveillance prior to these outbreaks, the genetic diversity and the transmission pathways of H5N1 viruses from this period remain undefined.
To determine the possible source of the wave 1 H5N1 viruses we recently conducted further sequencing and analysis of samples collected in live-poultry markets from Guangdong, Hunan and Yunnan in southern China from 2001 to 2004.
Phylogenetic analysis of the hemagglutinin and neuraminidase genes of 73 H5N1 isolates from this period revealed a greater genetic diversity in southern China than previously reported.
Moreover, results show that eight viruses isolated from Yunnan in 2002/2003 were most closely related to the Clade 1 virus sublineage from Vietnam, Thailand and Malaysia, while two viruses from Hunan in 2002/2003 were most closely related to viruses from Indonesia (Clade 2.1).
Further phylogenetic analyses of the six internal genes showed that all 10 of those viruses maintained similar phylogenetic relationships as the surface genes.
The 10 progenitor viruses were genotype Z and shared high similarity (>/=99%) with their corresponding descendent viruses in most gene segments.
These results suggest a direct transmission link for H5N1 viruses between Yunnan and Vietnam and also between Hunan and Indonesia during 2002/2003.
Poultry trade may be responsible for virus introduction to Vietnam, while the transmission route from Hunan to Indonesia remains unclear.
PMID: 18216109 [PubMed - as supplied by publisher]
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(1.7): Proc Natl Acad Sci U S A. 2008 Jan 23 [Epub ahead of print]
Lessons from the past: Familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918.
Gottfredsson M, Halld?rsson BV, J?nsson S, Kristj?nsson M, Kristj?nsson K, Kristinsson KG, L?ve A, Bl?ndal T, Viboud C, Thorvaldsson S, Helgason A, Gulcher JR, Stef?nsson K, J?nsd?ttir I.
Landspitali University Hospital, 108 Reykjavik, Iceland; Faculty of Medicine.
The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented.
It has been postulated that genetic host factors may have contributed to this high mortality.
We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts.
The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week.
Fatality proportions were highest among infants, young adults, and the elderly.
A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates.
The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution.
Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively.
The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively.
In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived.
Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.
PMID: 18216264 [PubMed - as supplied by publisher]
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(1.9): Vaccine. 2007 Dec 26 [Epub ahead of print]
Genetic and antigenic relatedness of H3 subtype influenza A viruses isolated from avian and mammalian species.
Yassine HM, Lee CW, Suarez DL, Saif YM.
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, United States.
In 2004, we isolated triple reassortant H3N2 influenza viruses from turkey breeder hens in Ohio and Illinois.
The Illinois flock was vaccinated twice with an inactivated H3N2 vaccine containing a swine origin virus before the outbreak.
Additionally, a commercial inactivated vaccine containing an H3N4 virus of duck origin is being used in some turkey breeders.
This prompted us to initiate a comparative study on the antigenic and genetic relatedness of various H3 subtype influenza viruses isolated from turkeys, ducks, pigs and humans.
The antigenic relatedness between the different viruses was evaluated with the Archetti and Horsfall formula, while nucleotide genetic similarities were calculated using pairwise alignments.
Results obtained indicated a high degree of antigenic (>90%) and genetic (>99%) similarities among the turkey-origin H3N2 viruses.
However, the turkey viruses were antigenically distantly related to the swine-origin vaccine virus (<30%), although they had approximately 95% genetic similarity in the HA1 gene.
Additionally, major genetic and antigenic changes were observed between the turkey viruses and the H3N4 duck vaccine virus as well as the H3N2 human virus.
Such genetic and antigenic differences between the turkey-origin viruses and other H3 subtype viruses including vaccine strains could be the reason for the failure in protection in the Illinois turkey breeders vaccinated with swine origin virus.
This also emphasizes the importance of using viruses for vaccines that are antigenically similar to the field strains.
PMID: 18206275 [PubMed - as supplied by publisher]
--
http://www.ncbi.nlm.nih.gov/sites/e...,18207290,18206275,17804108&dopt=AbstractPlus
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(1.2): J Immunol. 2008 Feb 1;180(3):1758-68.
Healthy Human Subjects Have CD4+ T Cells Directed against H5N1 Influenza Virus.
Roti M, Yang J, Berger D, Huston L, James EA, Kwok WW.
Benaroya Research Institute at Virginia Mason.
It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus.
In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection.
Adults born before 1968 have likely been exposed to H2N2 viruses.
We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes.
Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses.
Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/2004 (H5N1) virus.
These results are not surprising, because the matrix protein and nucleoprotein of influenza A viruses are conserved while the neuraminidase of the H5N1 virus is of the same subtype as that of the circulating H1N1 influenza strain.
However, H5N1 hemagglutinin-reactive CD4(+) T cells were also detected in 14 of 14 subjects examined despite the fact that hemagglutinin is less conserved.
Most were cross-reactive to H1, H2, or H3 hemagglutinin epitopes.
H5N1-reactive T cells were also detected ex vivo, exhibited a memory phenotype, and were capable of secreting IFN-gamma, TNF-alpha, IL-5, and IL-13.
These data demonstrate the presence of H5N1 cross-reactive T cells in healthy Caucasian subjects, implying that exposure to influenza A H1N1, H3N2, or H2N2 viruses through either vaccination or infection may provide partial immunity to the H5N1 virus.
PMID: 18209073 [PubMed - in process]
--
(1.5): J Virol. 2008 Jan 23 [Epub ahead of print]
Identification of the progenitors of Indonesia and Vietnam avian influenza A (H5N1) viruses from southern China.
Wang J, Vijaykrishna D, Duan L, Bahl J, Zhang JX, Webster RG, Peiris JS, Chen H, Smith GJ, Guan Y.
International Institute of Infection and Immunity, Shantou University, Shantou, Guangdong 515031, China; State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; Virology Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38015, USA.
The transmission of highly pathogenic avian influenza (HPAI) H5N1 virus to Southeast Asian countries triggered the first major outbreak and transmission wave in late 2003, accelerating the pandemic threat to the world.
Due to the lack of influenza surveillance prior to these outbreaks, the genetic diversity and the transmission pathways of H5N1 viruses from this period remain undefined.
To determine the possible source of the wave 1 H5N1 viruses we recently conducted further sequencing and analysis of samples collected in live-poultry markets from Guangdong, Hunan and Yunnan in southern China from 2001 to 2004.
Phylogenetic analysis of the hemagglutinin and neuraminidase genes of 73 H5N1 isolates from this period revealed a greater genetic diversity in southern China than previously reported.
Moreover, results show that eight viruses isolated from Yunnan in 2002/2003 were most closely related to the Clade 1 virus sublineage from Vietnam, Thailand and Malaysia, while two viruses from Hunan in 2002/2003 were most closely related to viruses from Indonesia (Clade 2.1).
Further phylogenetic analyses of the six internal genes showed that all 10 of those viruses maintained similar phylogenetic relationships as the surface genes.
The 10 progenitor viruses were genotype Z and shared high similarity (>/=99%) with their corresponding descendent viruses in most gene segments.
These results suggest a direct transmission link for H5N1 viruses between Yunnan and Vietnam and also between Hunan and Indonesia during 2002/2003.
Poultry trade may be responsible for virus introduction to Vietnam, while the transmission route from Hunan to Indonesia remains unclear.
PMID: 18216109 [PubMed - as supplied by publisher]
--
(1.7): Proc Natl Acad Sci U S A. 2008 Jan 23 [Epub ahead of print]
Lessons from the past: Familial aggregation analysis of fatal pandemic influenza (Spanish flu) in Iceland in 1918.
Gottfredsson M, Halld?rsson BV, J?nsson S, Kristj?nsson M, Kristj?nsson K, Kristinsson KG, L?ve A, Bl?ndal T, Viboud C, Thorvaldsson S, Helgason A, Gulcher JR, Stef?nsson K, J?nsd?ttir I.
Landspitali University Hospital, 108 Reykjavik, Iceland; Faculty of Medicine.
The pandemic influenza of 1918 (Spanish flu) killed 21-50 million people globally, including in Iceland, where the characteristics and spread of the epidemic were well documented.
It has been postulated that genetic host factors may have contributed to this high mortality.
We identified 455 individuals who died of the Spanish flu in Iceland during a 6-week period during the winter of 1918, representing >92% of all fatal domestic cases mentioned by historical accounts.
The highest case fatality proportion was 2.8%, and peak excess mortality was 162/100,000/week.
Fatality proportions were highest among infants, young adults, and the elderly.
A genealogical database was used to study relatedness and relative risk (RR) of the fatal influenza victims and relatives of their unaffected mates.
The significance of these RR computations was assessed by drawing samples randomly from the genealogical database matched for age, sex, and geographical distribution.
Familial aggregation of fatalities was seen, with RRs for death ranging from 3.75 for first-degree relatives (P < 0.0001) to 1.82 (P = 0.005), 1.12 (P = 0.252), and 1.47 (P = 0.0001) for second- to fourth-degree relatives of fatal influenza victims, respectively.
The RRs within the families of unaffected mates of fatal influenza victims were 2.95 (P < 0.0001), 1.27 (P = 0.267), 1.35 (P = 0.04), and 1.42 (P = 0.001), for first- to fourth-degree relatives, respectively.
In conclusion, the risk of death from the Spanish flu was similar within families of patients who succumbed to the illness and within families of their mates who survived.
Our data do not provide conclusive evidence for the role of genetic factors in susceptibility to the Spanish flu.
PMID: 18216264 [PubMed - as supplied by publisher]
--
(1.9): Vaccine. 2007 Dec 26 [Epub ahead of print]
Genetic and antigenic relatedness of H3 subtype influenza A viruses isolated from avian and mammalian species.
Yassine HM, Lee CW, Suarez DL, Saif YM.
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, United States.
In 2004, we isolated triple reassortant H3N2 influenza viruses from turkey breeder hens in Ohio and Illinois.
The Illinois flock was vaccinated twice with an inactivated H3N2 vaccine containing a swine origin virus before the outbreak.
Additionally, a commercial inactivated vaccine containing an H3N4 virus of duck origin is being used in some turkey breeders.
This prompted us to initiate a comparative study on the antigenic and genetic relatedness of various H3 subtype influenza viruses isolated from turkeys, ducks, pigs and humans.
The antigenic relatedness between the different viruses was evaluated with the Archetti and Horsfall formula, while nucleotide genetic similarities were calculated using pairwise alignments.
Results obtained indicated a high degree of antigenic (>90%) and genetic (>99%) similarities among the turkey-origin H3N2 viruses.
However, the turkey viruses were antigenically distantly related to the swine-origin vaccine virus (<30%), although they had approximately 95% genetic similarity in the HA1 gene.
Additionally, major genetic and antigenic changes were observed between the turkey viruses and the H3N4 duck vaccine virus as well as the H3N2 human virus.
Such genetic and antigenic differences between the turkey-origin viruses and other H3 subtype viruses including vaccine strains could be the reason for the failure in protection in the Illinois turkey breeders vaccinated with swine origin virus.
This also emphasizes the importance of using viruses for vaccines that are antigenically similar to the field strains.
PMID: 18206275 [PubMed - as supplied by publisher]
--
http://www.ncbi.nlm.nih.gov/sites/e...,18207290,18206275,17804108&dopt=AbstractPlus
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