Evidence for antibody as a protective correlate for COVID-19 vaccines

Earle, Kristen A.; Ambrosino, Donna M.; Fioré-Gartland, Andrew; Goldblatt, David; Gilbert, Peter B.; Siber, George R.; Dull, Peter; Plotkin, Stanley А.

doi:10.1101/2021.03.17.20200246

Cited by 144 publications

(206 citation statements)

References 3 publications

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“…At week 22, 18 weeks after the 2 nd dose, median ID 50 titers in the pseudovirus assay still exceeded 10 3 for the protein vaccine group and 10 2 for the mRNA group. The immune correlates of protection against SARS-CoV-2 infection and disease still need to be conclusively determined (58,59). To address this question, McMahan et al (48) adoptively transferred plasma IgG from adult SARS-CoV-2 convalescent rhesus macaques and determined that a S proteinspecific reciprocal endpoint dilution ELISA titer of 400 and pseudovirus neutralizing antibody (ID50) titers of approximately 50 can protect adult rhesus macaques against combined intratracheal and intranasal SARS-CoV-2 challenge (48).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

et al. 2021

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The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

et al. 2021

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“…Although an immune correlate of protection against COVID-19 has not been established yet, levels of virus-specific binding and neutralizing Ab have been shown to correlate with vaccine efficacy in phase 3 studies across different vaccination platforms [28]. In addition, data from pre-clinical studies on nonhuman primates indicate that mRNA vaccine-induced neutralizing Ab can mediate protection against disease [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes

Pannus

Neven

Craeye

et al. 2021

Preprint

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Background Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. Methods Forty residents and forty staff members either naïve or previously infected with SARS-CoV-2 were recruited in two NH in Belgium before immunization with two doses of 30μg BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 variant were assessed at days 0, 21, 28, and 49. Results SARS-CoV-2 naïve residents had lower Ab responses to BNT162b2 mRNA vaccination than naïve staff. These poor responses involved lower levels of IgG to all domains of the vaccine antigen, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naïve resident had detectable neutralizing Ab to the B.1.351 variant. High and comparable Ab responses were observed in residents and staff previously infected with SARS-CoV-2. Clustering analysis revealed that poor vaccine responders not only included naïve residents but also naïve staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. Conclusions The poor Ab responses to mRNA vaccination observed in infection naïve residents and in some naïve staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. Adapted vaccination regimens may be needed to provide optimal protection against COVID-19 to vulnerable populations.

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“…Evidence is mounting that neutralizing antibodies acquired by natural infection (32,33) or through vaccination (34,35) are a correlate of protection against COVID-19. Therefore, it will be critical to assess whether and how VRVs and/or VRV-haplotypes in the infecting strains impact neutralizing antibody titers attained by natural infection (36), as well as whether and how they impact neutralization sensitivity to vaccine-induced neutralizing antibodies (12) and/or monoclonal antibodies (37).…”

Section: Discussionmentioning

confidence: 99%

Tracking SARS-CoV-2 Spike Protein Mutations in the United States (2020/01 – 2021/03) Using a Statistical Learning Strategy

Zhao

Lybrand

Gilbert

et al. 2021

Preprint

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The emergence and establishment of SARS-CoV-2 variants of interest (VOI) and variants of concern (VOC) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from US COVID-19 cases (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from January 19, 2020 to March 15, 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics, to identify VRVs with significant and substantial dynamics (false discovery rate q-value <0.01; maximum VRV proportion > 10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modelling was performed to gain insight into potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which have not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identifies 17 VRVs ~91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of 4 VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods.

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Evidence for antibody as a protective correlate for COVID-19 vaccines

Cited by 144 publications

References 3 publications

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes

Tracking SARS-CoV-2 Spike Protein Mutations in the United States (2020/01 – 2021/03) Using a Statistical Learning Strategy

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