Table Info

Table 1.

Correlates titer of protection against SARS-CoV-2 proposed by different study groups

Authors, reference	Type of study	Design	Subjects, participants	Methods for anti-SARS-CoV-2 antibodies detection, units	Proposed correlate titer of protection (units)
Corbett et al. [53]	Animal model	mRNA-1273 vaccine	Non-human primates	IU/mL	No animal with S-specific IgG > 336 IU/mL had BAL subgenomic RNA (sgRNA) > 10,000 copies/mL, and no animal with S-specific IgG > 645 IU/mL had NS sgRNA > 100,000 copies/swab, so these were chosen as the thresholds for protection
Sui et al. [50]	Animal model	Vaccine ChAdOx1 nCov-19 Ad26 COV2.S mRNA-1273 BBIBP-CorV PiCovacc DNA	Non-human primates	Ab-pseudo/live Nab	10-160/N/A 408/113 1862/3481 N/A/200 N/A/10–100 N/A/74
Feng et al. [37]	Randomized single-blind vaccine efficacy trial	ChAdOx1 nCoV-19 vaccine	Humans	For 90% VE: anti-S IgG: 899 (369, NC), BAU/mL; Anti-RBD IgG: 2360 (723, NC) BAU/mL Normalized live-virus neutralization assay: 938 (294, NC) NF₅₀ Pseudovirus neutralization assay: 140 (43, NC) IU/mL A vaccine efficacy of 80% against symptomatic infection with majority alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 BAU/mL: and 506 BAU/mL for anti-S and anti-RBD antibodies, and 26 IU/mL and 247 normalized neutralization titers (NF₅₀) for pseudovirus and live-virus neutralization, respectively	For 80% VE against primary symptomatic COVID-19, for anti-S IgG, was a level of 264 BAU/mL For anti-RBD IgG, 80% efficacy was achieved with a median antibody level of 506 BAU/mL (95% CI: 135, NC)
Lau et al. [8]	Cohort study	Immunity 90 days after infection with SARS-COV-2/convalescence	Human	N/A Neutralizing antibody is clearly one major correlate of protection, but the titers associated with protection from re-infection are not precisely defined	The threshold for 50% protection from re-infection for PRNT₅₀ and PRNT₉₀ were 1:25.9 (95% CI 1:24.7–1:27.6) and 1:8.9 (95% CI 1:8.6–1:9.4) respectively 50% of patients who recover from symptomatic SARS-CoV would be protected from re-infection for 701 days based on PRNT₉₀ titers or 990 days as estimated by PRNT₅₀ titers
Meschi et al. [54]	Observational study	Antibody response to an mRNA vaccine	Human, 120 vaccinated HCW and 94 previously infected	N/A Quantitative anti-RBD and virus microneutralization test for robust (≥ 1:80) MNT titer A threshold of 2,000 BAU/mL is highly predictive of strong MNT response in vaccinated individuals and may represent a good surrogate marker of a protective response	Correlation between BAU and MNT titers (MNT titer (≥ 1:80) was reached at 1,814 and 3,564 BAU/mL)
Bates et al. [55]	Cohort study	Vaccine/convalescence	Human, vaccinated and previously infected	N/A	Escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough
Earle et al. [47]	Statistical analysis	Vaccine	Human	N/A	Antibody titers correlated with efficacy across seven different vaccines; where higher titers correlated with higher vaccine efficacy, despite other uncontrolled variables
Khoury et al. [10]	Statistical analysis	Vaccine	Human	N/A	Despite the known inconsistencies between studies, a comparison of normalized neutralization levels and vaccine efficacy demonstrated a remarkably strong non-linear relationship between mean neutralization level and the reported protection across different vaccines
Dimeglio et al. [48]	Cohort study	Vaccinated/unvaccinated/convalescence	Humans, 8758 HCWs	NAb titer ≥ 256 was associated with full (100%) protection ELISA-concentration of 1,700 BAU/mL and above provided full protection	The thresholds of protection should be confirmed in further studies on other populations. Antibody’s reduced neutralizing capacity against new emerging VOC should be tested
van der Lubbe et al. [45]	Animal model	Vaccine	Syrian hamsters	Nab protective titer between 64–128 ELISA log₁₀ between 3.5–4	Hamsters were classified either as infected or protected from SARS-CoV-2, defined as a lung viral load of either above or below 102 TCID50/g, respectively
Tostanoski et al. [46]	Animal model	Vaccine	70 Syrian golden hamsters	RBD-specific binding antibodies were assessed by ELISA	A significant correlation was found between ab titer and lower viral load
Yu et al. [50]	Animal model	Vaccine	Rhesus macaques, non-human primates	Log Nab titer	Log Nab titer above 2.0 provided complete protection
McMahan et al. [3]	Animal model	Convalescent	Non-human primates (31 rhesus macaques)	NAb titres	NAb titers of approximately 500 fully protected macaques, and titers of approximately 50 partially protected macaques. These titers should be readily achievable by vaccination in humans. These data demonstrate that relatively low NAb titers are sufficient to protect against SARS-CoV-2 in rhesus macaques
Haveri et al. [56]	Observational study	Convalescense	Humans	Nab	NAb against the WT virus persisted in 89% and S-IgG in 97% of subjects for at least 13 months after infection. Only 36% had N-IgG by 13 months. The mean S-IgG concentrations declined from 8 to 13 months by less than one-third; N-IgG concentrations declined by two-thirds
Xiang et al. [39]	Observational study	Convalescent COVID-19 patients	Humans	Virus neutralizing Ab	After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies against nucleocapsid antigen and RBD-S. Neutralizing activity was detectable in ~43% of patients with a reduction of virus-neutralizing capacity of 22.6% to VOC

NC: not computed; BAL: broncho-alveolar lavage; Ab: antobodies; VE: vaccine efficacies; NF₅₀: normalized live-virus neutralization titer; N/A: not applicable; MNT: minimal neutralizing titer; WT: wild type; PRNT₅₀: plaque reduction neutralization at 50% neutralization endpoint; PRNT₉₀: plaque reduction neutralization at 90% neutralization endpoint; NS: non-significant

Declarations

Author contributions

YS and TV contributed conception and design of the study; DG and NI searched and organized the existing papers on the topic in a database; YS organized the table; TV crafted the figure; YS wrote the first draft of the manuscript; DG, NI, and TV wrote sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

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Copyright

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