| dc.description.abstract | A Sendai Virus (Sev) vector is being developed for 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, US 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
<1,000 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.
be the best long-term intervention to reduce the spread of HIV.
Current AIDS vaccine candidates either fail to induce neutralizing
antibodies or induce antibodies that neutralize a very
restricted range primary HIV isolates2 which represents a major
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, US 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
<1,000 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. | en |
