TY - JOUR
T1 - An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination
AU - Carreño, Juan Manuel
AU - Raskin, Ariel
AU - Singh, Gagandeep
AU - Tcheou, Johnstone
AU - Kawabata, Hisaaki
AU - Gleason, Charles
AU - Srivastava, Komal
AU - Vigdorovich, Vladimir
AU - Dambrauskas, Nicholas
AU - Gupta, Sneh Lata
AU - Domínguez, Irene González
AU - Martinez, Jose Luis
AU - Slamanig, Stefan
AU - Sather, D. Noah
AU - Raghunandan, Rama
AU - Wirachwong, Ponthip
AU - Muangnoicharoen, Sant
AU - Pitisuttithum, Punnee
AU - Wrammert, Jens
AU - Suthar, Mehul S.
AU - Sun, Weina
AU - Palese, Peter
AU - García-Sastre, Adolfo
AU - Simon, Viviana
AU - Krammer, Florian
N1 - Funding Information:
We thank the study participants of the vaccine trial, the PARIS cohort, and our longitudinal observational cohort for generosity and willingness to help advance our knowledge on SARS-CoV-2 immune responses. We thank R. A. Albrecht for oversight of the conventional BSL-3 biocontainment facility at Mount Sinai, which makes our work with live SARS-CoV-2 possible. We are also grateful for Mount Sinai’s leadership during the COVID-19 pandemic. We want to especially thank D. Charney, D. Reich, and K. Davis for support. We also would like to thank the teams at PATH, Mahidol University, and the Government Pharmaceutical Organization for support. This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (to F.K.). In addition, this work was also partially funded by the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract and 75N93021C00014 (to A.G.-S.) and 75N93021C00017 (to M.S.S.) and by anonymous donations to Mount Sinai (to F.K.). Work on NDV-HXP-S vaccines was also supported by the Bill & Melinda Gates Foundation (to P. Palese) and by institutional funding from the Icahn School of Medicine at Mount Sinai (to P. Palese). PATH funded the shipment of samples from Nexelis to Mount Sinai. The main NDV-HXP-S project in Thailand is funded by the National Vaccine Institute, Government Pharmaceutical Organization.
Publisher Copyright:
Copyright © 2023 The Authors.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - NDV-HXP-S is a recombinant Newcastle disease virus–based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.
AB - NDV-HXP-S is a recombinant Newcastle disease virus–based vaccine against SARS-CoV-2, which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that used for the production of the vast majority of influenza virus vaccines. Here, we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a phase 1 clinical study in Thailand. The SARS-CoV-2 neutralizing and spike protein binding activity of NDV-HXP-S postvaccination serum samples was compared to that of samples from mRNA BNT162b2 (Pfizer) vaccinees. Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of BNT162b2 vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccinees. This led us to calculate ratios between binding and neutralizing antibody titers. Samples from NDV-HXP-S vaccinees had binding to neutralizing activity ratios that were lower than those of BNT162b2 sera, suggesting that NDV-HXP-S vaccination elicits a high proportion of neutralizing antibodies and low non-neutralizing antibody titers. Further analysis showed that, in contrast to mRNA vaccination, which induces strong antibody titers to the receptor binding domain (RBD), the N-terminal domain, and the S2 domain, NDV-HXP-S vaccination induced an RBD-focused antibody response with little reactivity to S2. This finding may explain the high proportion of neutralizing antibodies. In conclusion, vaccination with inactivated NDV-HXP-S induces a high proportion of neutralizing antibodies and absolute neutralizing antibody titers that are comparable to those elicited by mRNA vaccination.
UR - http://www.scopus.com/inward/record.url?scp=85148114566&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abo2847
DO - 10.1126/scitranslmed.abo2847
M3 - Article
C2 - 36791207
AN - SCOPUS:85148114566
SN - 1946-6234
VL - 15
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 683
M1 - eabo2847
ER -