Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.
The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 v...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2009
|
| _version_ | 1826274671117467648 |
|---|---|
| author | Fan, S Gao, Y Shinya, K Li, C Li, Y Shi, J Jiang, Y Suo, Y Tong, T Zhong, G Song, J Zhang, Y Tian, G Guan, Y Xu, X Bu, Z Kawaoka, Y Chen, H Xu, X |
| author_facet | Fan, S Gao, Y Shinya, K Li, C Li, Y Shi, J Jiang, Y Suo, Y Tong, T Zhong, G Song, J Zhang, Y Tian, G Guan, Y Xu, X Bu, Z Kawaoka, Y Chen, H Xu, X |
| author_sort | Fan, S |
| collection | OXFORD |
| description | The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N1 virus A/VN/1203/2004 (clade 1) was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca) that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05) (clade 2.3), and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca). AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2). These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials. |
| first_indexed | 2024-03-06T22:47:00Z |
| format | Journal article |
| id | oxford-uuid:5d85f545-29f8-48ea-af88-dce89397147d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:47:00Z |
| publishDate | 2009 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:5d85f545-29f8-48ea-af88-dce89397147d2022-03-26T17:34:59ZImmunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5d85f545-29f8-48ea-af88-dce89397147dEnglishSymplectic Elements at OxfordPublic Library of Science2009Fan, SGao, YShinya, KLi, CLi, YShi, JJiang, YSuo, YTong, TZhong, GSong, JZhang, YTian, GGuan, YXu, XBu, ZKawaoka, YChen, HXu, XThe continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N1 virus A/VN/1203/2004 (clade 1) was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca) that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05) (clade 2.3), and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca). AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2). These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials. |
| spellingShingle | Fan, S Gao, Y Shinya, K Li, C Li, Y Shi, J Jiang, Y Suo, Y Tong, T Zhong, G Song, J Zhang, Y Tian, G Guan, Y Xu, X Bu, Z Kawaoka, Y Chen, H Xu, X Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title | Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title_full | Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title_fullStr | Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title_full_unstemmed | Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title_short | Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. |
| title_sort | immunogenicity and protective efficacy of a live attenuated h5n1 vaccine in nonhuman primates |
| work_keys_str_mv | AT fans immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT gaoy immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT shinyak immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT lic immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT liy immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT shij immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT jiangy immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT suoy immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT tongt immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT zhongg immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT songj immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT zhangy immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT tiang immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT guany immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT xux immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT buz immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT kawaokay immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT chenh immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates AT xux immunogenicityandprotectiveefficacyofaliveattenuatedh5n1vaccineinnonhumanprimates |