Prevalence of specific neutralizing antibodies against Sendai virus in populations from different geographic areas: Implications for AIDS vaccine development using Sendai virus vectors

A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will aff...

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Published inHuman vaccines Vol. 7; no. 6; pp. 639 - 645
Main Authors Hara, Hiroto, Hironaka, Takashi, Inoue, Makoto, Iida, Akihiro, Shu, Tsugumine, Hasegawa, Mamoru, Nagai, Yoshiyuki, Falsey, Ann R., Kamali, Anatoli, Anzala, Omu, Sanders, Eduard J., Karita, Etienne, Mwananyanda, Lawrence, Vasan, Sandhya, Lombardo, Angela, Parks, Christopher L., Sayeed, Eddy, Krebs, Marietta, Cormier, Emmanuel, Ackland, James, Price, Matthew A., Excler, Jean-Louis
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.06.2011
Subjects
Adolescent
Adult
Africa
AIDS Vaccines - immunology
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cross Reactions
Cycle
Europe
Female
Genetic Vectors
Humans
Japan
Landes
Male
Middle Aged
Organogenesis
Parainfluenza Virus 1, Human - immunology
Proteins
Sendai virus - genetics
Sendai virus - immunology
United States
United States
Europe
Japan
Africa
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Abstract A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers
AbstractList A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers
A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers < 1000 with 71.7% < 100 (< 5 considered negative). There was no significant difference in titer or prevalence by gender, age range or geographic origin. However, African males had a lower titer than non-Africans of either gender (p=0.007). Overall, the prevalence of SeV NAb is high and likely due to neutralization by cross-reactive hPIV-1 antibodies. Clinical trials will be needed to assess the influence of pre-existing SeV NAb on HIV-specific immune responses elicited by a SeV vaccine vector expressing HIV.
A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers < 1000 with 71.7% < 100 (< 5 considered negative). There was no significant difference in titer or prevalence by gender, age range or geographic origin. However, African males had a lower titer than non-Africans of either gender (p=0.007). Overall, the prevalence of SeV NAb is high and likely due to neutralization by cross-reactive hPIV-1 antibodies. Clinical trials will be needed to assess the influence of pre-existing SeV NAb on HIV-specific immune responses elicited by a SeV vaccine vector expressing HIV.A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers < 1000 with 71.7% < 100 (< 5 considered negative). There was no significant difference in titer or prevalence by gender, age range or geographic origin. However, African males had a lower titer than non-Africans of either gender (p=0.007). Overall, the prevalence of SeV NAb is high and likely due to neutralization by cross-reactive hPIV-1 antibodies. Clinical trials will be needed to assess the influence of pre-existing SeV NAb on HIV-specific immune responses elicited by a SeV vaccine vector expressing HIV.
Author Hara, Hiroto
Parks, Christopher L.
Hasegawa, Mamoru
Mwananyanda, Lawrence
Nagai, Yoshiyuki
Ackland, James
Anzala, Omu
Shu, Tsugumine
Karita, Etienne
Inoue, Makoto
Falsey, Ann R.
Kamali, Anatoli
Sayeed, Eddy
Krebs, Marietta
Vasan, Sandhya
Lombardo, Angela
Price, Matthew A.
Cormier, Emmanuel
Hironaka, Takashi
Sanders, Eduard J.
Iida, Akihiro
Excler, Jean-Louis
AuthorAffiliation Centre for Geographic Medicine Research-Coast; Kenya Medical Research Institute (KeMRI); Kilifi, Kenya
Aaron Diamond AIDs Research Center; New York, NY USA
Rwanda-Zambia HIV Research Group; Lusaka, Zambia
International AIDS Vaccine Initiative; New York, NY USA
DNAVEC Corporation; Tsukuba, Ibaraki Japan
Rochester General Hospital; Rochester, NY USA
Centre for Clinical Vaccinology and Tropical Medicine; University of Oxford; Headington, UK
RIKEN Center of Research Network for Infectious Diseases
Rwanda-Zambia HIV Research Group; Kigali, Rwanda
IAVI Human Immunology Laboratory; Imperial College; London, UK
Kenya AIDS Vaccine Initiative; University of Nairobi; Nairobi, Kenya
Medical Research Council; Uganda Virus Research Institute; Uganda Research Unit on AIDS; Entebbe, Uganda
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Snippet A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and...
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SubjectTerms Adolescent
Adult
Africa
AIDS Vaccines - immunology
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cross Reactions
Cycle
Europe
Female
Genetic Vectors
Humans
Japan
Landes
Male
Middle Aged
Organogenesis
Parainfluenza Virus 1, Human - immunology
Proteins
Sendai virus - genetics
Sendai virus - immunology
United States
Title Prevalence of specific neutralizing antibodies against Sendai virus in populations from different geographic areas: Implications for AIDS vaccine development using Sendai virus vectors
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http://www.landesbioscience.com/journals/vaccines/article/15408/
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Volume 7
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