Detection of pre-existing neutralizing antibodies against Ad26 in HIV-1-infected individuals not responding to the Ad26.COV2.S vaccine

检测对 Ad26.COV2.S 疫苗无反应的 HIV-1 感染者体内预先存在的针对 Ad26 的中和抗体

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作者:Katja G Schmidt, Ellen G Harrer, Verena Schönau, David Simon, Arnd Kleyer, Philipp Steininger, Klaus Korn, Georg Schett, Carina S Knobloch, Krystelle Nganou-Makamdop #, Thomas Harrer #

Conclusion

Ad26.COV2.S vaccination showed a high failure rate in HIV-1-infected patients. Pre-existing immunity against Ad26 could be an important contributor to poor vaccine efficacy in a subgroup of patients.

Methods

We included all Ad26.COV2.S vaccinated HIV-1-infected patients of Erlangen HIV cohort fulfilling all inclusion criteria. The study cohort consisted of 15 HIV-1-infected patients and three HIV-1-uninfected subjects who received the Ad26.COV2.S vaccine between April and November 2021. Pre-vaccination sera were collected between October 2014 and June 2021, post-vaccination sera between June and December 2021. Neutralizing antibodies towards Ad26 were determined by a FACS-based inhibition assay measuring the expression of SARS-CoV-2 spike and adenoviral proteins in HEK293T cells after in-vitro transduction with Ad26.COV2.S or the control ChAdOx1-S.

Purpose

The Ad26.COV2.S vaccine is a replication-incompetent human adenovirus type 26 vector encoding the SARS-CoV-2 spike protein. In a phase 1-2a trial, a single dose of Ad26.COV2.S induced SARS-CoV-2 spike-specific antibodies in ≥ 96% of healthy adults. To investigate vaccine immunogenicity in HIV-1-infection, we measured SARS-CoV-2 spike-specific antibodies in Ad26.COV2.S vaccinated HIV-1-infected patients and analyzed the presence of pre-existing Ad26 neutralizing antibodies.

Results

Six out of 15 HIV-1-infected patients failed to develop SARS-CoV-2-specific antibodies and four patients developed weak antibody responses after vaccination with Ad26.COV2.S. Pre-vaccination sera of four of the six vaccine non-responders showed neutralizing activity towards Ad26.COV2.S but not toward the ChAdOx1-S vaccine at 1:50 dilution. After Ad26.COV2.S vaccination, 17 of the 18 subjects developed strong Ad26-neutralizing activity and only one of the 18 subjects showed neutralizing activity towards the ChAdOx1-S vaccine.

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