SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Roozendaal, Ramon; Solforosi, Laura; Stieh, Daniel J.; Serroyen, Jan; Straetemans, Roel; Wegmann, Frank; Huber, Sietske K. Rosendahl; Lubbe, Joan E. M. van der; Hendriks, Jenny; Gars, Mathieu Le; Dekking, Liesbeth; Czapska-Casey, Dominika; Guimerà, Núria; Janssen, Sarah; Tete, Sarah M.; Chandrashekar, Abishek; Mercado, Noe B.; Yu, Jingyou; Koudstaal, Wouter; Sadoff, Jerry; Barouch, Dan H.; Schuitemaker, Hanneke; Zahn, Roland

doi:10.1101/2021.01.30.428921

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…It is possible that the suboptimal responses we observed may improve after 3 weeks in older individuals. Even if this is the case, individuals over 80 are nonetheless likely to be at prolonged increased risk for infection, based on studies in non-human primates linking protection from SARS-CoV-2 challenge with neutralising antibody titres, but not T cell responses 11,12 . In further support for the role of neutralising antibodies are two clinical studies: (i) use of early convalescent sera in COVID-19 disease within elderly patients demonstrating improved clinical outcomes 13 and (ii) the recent report of suboptimal efficacy of the ChAdOx nCov-19 vaccine against prevention of mild to moderate COVID-19 in the context of the variant 501Y.V3 (http://www.theguardian.com/society/2021/feb/07/covid-vaccine-booster-variants-emerge-minister).…”

Section: Discussionmentioning

confidence: 99%

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

Collier

Ferreira

Datir

et al. 2021

Preprint

119

114

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Vaccines remain the cornerstone for containing the SARS-CoV-2 pandemic. mRNA vaccines provide protection in clinical trials using a two-dose approach, separated by a three-week gap. Here we assessed real world immune responses following vaccination with mRNA-based vaccine BNT162b2. Following the first and second doses of the BNT162b2 vaccine, we measured IFNgamma; T cell responses, both total IgG Spike, IgG Spike RBD and neutralising antibody responses to Spike in sera using a lentiviral pseudotyping system. Median age was 82 amongst 26 participants. Three weeks after the first dose a lower proportion of participants over 80 years old achieved adequate neutralisation titre of >1:4 for 50% neutralisation as compared to those under 80 (8/15 versus 11/11, p<0.05). Mean neutralisation titres in this age group after the first dose were lower than in younger individuals (p<0.05). Following the second dose, neutralising antibody response 50% titres were above 1:4 in all individuals and there was no longer a difference by age grouping. A significant proportion of individuals over 80 appear to require a second dose of vaccine, given in this study at three weeks, to achieve virus neutralisation.

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Section: Discussionmentioning

confidence: 99%

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

Collier

Ferreira

Datir

et al. 2021

Preprint

119

114

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“…The proportion of individuals over 80 years old with poor neutralisation responses did not change between 3 and 12 weeks after the first dose. This argues against increased responses after 3 weeks for the Pfizer vaccine and indicates prolonged increased risk for infection in this group 8,37 . Although the second dose was able to boost neutralising antibodies, SARS-CoV-2 infection during an enlarged window period between doses in the presence of only partially protective antibody titres could also lead to favourable conditions for selecting escape mutations in populations such as the elderly who are also clinically vulnerable to severe disease 38,39 .…”

Section: Discussionmentioning

confidence: 99%

Age-related heterogeneity in immune responses to SARS-CoV-2 following BNT162b2 vaccination

Ferreira¹,

Datir²,

Kotagiri³

et al. 2021

Preprint

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Vaccines remain the cornerstone for containing the SARS-CoV-2 pandemic. mRNA vaccines provide protection in clinical trials using a two-dose approach, separated by a three to four week gap. UK policy in 2021 is to extend the dosing interval from three to twelve weeks and other countries are likely to follow suit given the demand for mRNA vaccines and ongoing uncontrolled transmission. There is a paucity of data in the elderly, even though these individuals are the first to receive vaccines due to risk of severe disease. Here we assessed real world immune responses following vaccination with mRNA-based vaccine BNT162b2. Median age was 81 years amongst 101 participants after the first dose of the BNT162b2 vaccine. Geometric mean neutralisation titres in participants over 80 years old after the first dose were lower than in younger individuals [83.4 (95% CI 52.0-133.7) vs 46.6 (95% CI 33.5-64.8) p 0.01]. A lower proportion of participants 80 years and older achieved adequate neutralisation titre of >1:20 for 50% neutralisation as compared to those under 80 (21% vs 51%, p 0.003). Binding IgG responses correlated with neutralisation. Sera from participants in both age groups showed significantly lower neutralisation potency against B.1.1.7 Spike pseudotyped viruses as compared to wild type. The adjusted ORs for inadequate neutralisation in the 80 years and above age group were 3.7 (95% CI 1.2-11.2) and 4.4 (95% CI 1.5-12.6) against wild type and B.1.1.7 pseudotyped viruses. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T- cell IFN𝛾 and IL-2 responses were impaired in the older age group after 1 dose and although IFN𝛾 increased between vaccine doses, IL-2 responses did not significantly increase. There was a significantly higher risk of suboptimal neutralising antibody and T cell response following first dose vaccination with BNT162b2 in half of participants above the age of 80, persisting up to 12 weeks. These high risk populations warrant specific measures in order to mitigate against vaccine failure, particularly where SARS-CoV-2 variants of concern are circulating.

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“…It is a recombinant adenovirus serotype 26 vector encoding SARS-CoV-2 peplomers based on SARS-CoV-2 Wuhan-Hu-1 isolate strain (Genbank accession number: MN908947) [ 135 ]. Ad26.COV2 demonstrated high efficacy under preclinical setting in multiple animal models, including Syrian hamster, non-human primates, in which all vaccinated animals showed a rapid increase in neutralizing antibodies and reduction in lung viral load [ 136 , 137 , 138 , 139 ]. Notably, all animal models reported the absence of any adverse side effects or signs of vaccine-related respiratory disease, suggestive of a safe and tolerable vaccine candidate against SARS-CoV-2 [ 136 , 137 , 138 , 139 ].…”

Section: Covid-19 Vaccine Developmentmentioning

confidence: 99%

“…Ad26.COV2 demonstrated high efficacy under preclinical setting in multiple animal models, including Syrian hamster, non-human primates, in which all vaccinated animals showed a rapid increase in neutralizing antibodies and reduction in lung viral load [ 136 , 137 , 138 , 139 ]. Notably, all animal models reported the absence of any adverse side effects or signs of vaccine-related respiratory disease, suggestive of a safe and tolerable vaccine candidate against SARS-CoV-2 [ 136 , 137 , 138 , 139 ]. Under clinical setting, safety and tolerability trial (NCT04436276) exhibited high safety and efficacy profile of Ad26.COV2 in human participants, with elevated neutralizing antibody response of 88% in the adult population (aged 18–55) and 93% in the elderly population (aged > 65) without any significant adverse events reported [ 140 ].…”

Section: Covid-19 Vaccine Developmentmentioning

confidence: 99%

An Appraisal of the Current Scenario in Vaccine Research for COVID-19

Chong

Chellappan

Shukla

et al. 2021

Viruses

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The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.

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SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Cited by 8 publications

References 18 publications

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2

Age-related heterogeneity in immune responses to SARS-CoV-2 following BNT162b2 vaccination

An Appraisal of the Current Scenario in Vaccine Research for COVID-19

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