COVID-19 vaccines: neutralizing antibodies and the alum advantage

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Abstract

Achieving high levels of neutralizing antibodies to the spike protein of SARS-CoV-2 in a safe manner is likely to be crucial for an effective vaccine. Here, we propose that aluminium-based adjuvants might hold the key to this.

Abstract

Here, Peter Hotez and colleagues discuss the advantages of using an aluminium-based adjuvant in candidate COVID-19 vaccines.

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Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

Feng-Cai Zhu, Yu-Hua Li, Xu-Hua Guan … (2020)

Summary Background A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Methods We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Findings Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. Funding National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

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DNA vaccine protection against SARS-CoV-2 in rhesus macaques

Jingyou Yu, Lisa H. Tostanoski, Lauren Peter … (2020)

The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

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Rapid COVID-19 vaccine development

Barney S. Graham (2020)

Finding the fastest pathway to vaccine availability includes the avoidance of safety pitfalls

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Author and article information

Contributors

Peter J. Hotez: hotez@bcm.edu

David B. Corry: dcorry@bcm.edu

Ulrich Strych:

ORCID: http://orcid.org/0000-0001-9455-7683

strych@bcm.edu

Maria Elena Bottazzi:

ORCID: http://orcid.org/0000-0002-8429-0476

bottazzi@bcm.edu

Journal

Journal ID (nlm-ta): Nat Rev Immunol

Journal ID (iso-abbrev): Nat. Rev. Immunol

Title: Nature Reviews. Immunology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1474-1733

ISSN (Electronic): 1474-1741

Publication date (Electronic): 4 June 2020

Pages: 1-2

Affiliations

[1 ]Texas Children’s Center for Vaccine Development, Houston, TX USA

[2 ]ISNI 0000 0001 2160 926X, GRID grid.39382.33, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, , Baylor College of Medicine, ; Houston, TX USA

[3 ]ISNI 0000 0001 2111 2894, GRID grid.252890.4, Department of Biology, , Baylor University, ; Waco, TX USA

[4 ]ISNI 0000 0004 4687 2082, GRID grid.264756.4, Hagler Institute for Advanced Study at Texas A&M University, ; College Station, TX USA

[5 ]ISNI 0000 0001 2160 926X, GRID grid.39382.33, Departments of Medicine (Immunology, Allergy and Rheumatology) and Pathology & Immunology, , Baylor College of Medicine, ; Houston, TX USA

[6 ]Michael E. DeBakey VA Center for Translational Research in Inflammatory Diseases, Houston, TX USA

Author information

Ulrich Strych http://orcid.org/0000-0001-9455-7683

Maria Elena Bottazzi http://orcid.org/0000-0002-8429-0476

Article

Publisher ID: 358

DOI: 10.1038/s41577-020-0358-6

PMC ID: 7271131

PubMed ID: 32499636

SO-VID: e2f9b5c1-d1cb-4671-8121-3a36da65c890

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

COVID-19 vaccines: neutralizing antibodies and the alum advantage

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Most cited references 10

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial

DNA vaccine protection against SARS-CoV-2 in rhesus macaques

Rapid COVID-19 vaccine development

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