key: cord-0277755-93tcce65
authors: Leys, Y. E.; Nwokocha, M.; Walker, J. P.; Butterfield, T. R.; Frater, V.; Thompson, T. K.; Anderson, M.; Cloherty, G. A.; Anzinger, J. J.
title: SARS-CoV-2 Receptor Binding Domain IgG Response to AstraZeneca (AZD1222) COVID-19 Vaccination, Jamaica
date: 2021-10-25
journal: nan
DOI: 10.1101/2021.10.22.21265401
sha: 423527ca7a5029101ed88c53834d4c70c96ad0e4
doc_id: 277755
cord_uid: 93tcce65

The Caribbean region is lacking an assessment of the antibody response and side effects experienced after AstraZeneca COVID-19 vaccination (AZD1222). We examined SARS-CoV-2 spike receptor binding domain (RBD) IgG levels and reported side effects in a Jamaican population after AZD1222 vaccination. Median RBD IgG levels for persons without evidence of previous SARS-CoV-2 infection were 43.1 bIU/mL after 3-7 weeks post first dose, rising to 100.1 bIU/mL 3-7 weeks post second dose, and falling 46.9 bIU/mL 16-22 weeks post second dose. The median RBD IgG level 2-8 weeks after symptom onset for unvaccinated SARS-CoV-2 infected persons of all disease severities was 411.6 bIU/mL. Common AZD1222 side effects after first dose were injection site pain, headache and chills. Most persons reported no side effects after second dose. AZD1222 is widely used across the English-speaking Caribbean and the study provides evidence for its continued safe and effective use in vaccination programs.

The Caribbean region is lacking an assessment of the antibody response and side effects 30 experienced after AstraZeneca COVID-19 vaccination (AZD1222). We examined SARS-CoV-2 31 spike receptor binding domain (RBD) IgG levels and reported side effects in a Jamaican 32 population after AZD1222 vaccination. Median RBD IgG levels for persons without evidence of 33 previous SARS-CoV-2 infection were 43.1 bIU/mL after 3-7 weeks post first dose, rising to 34 100.1 bIU/mL 3-7 weeks post second dose, and falling 46.9 bIU/mL 16-22 weeks post second 35 dose. The median RBD IgG level 2-8 weeks after symptom onset for unvaccinated SARS-CoV-2 36 infected persons of all disease severities was 411.6 bIU/mL. Common AZD1222 side effects 37 after first dose were injection site pain, headache and chills. Most persons reported no side 38 effects after second dose. AZD1222 is widely used across the English-speaking Caribbean and 39 the study provides evidence for its continued safe and effective use in vaccination programs. 40 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 Antibody responses to vaccination were determined using an Abbott ARCHITECT i2000sr 64 instrument (Abbott Laboratories, Abbott Park, Illinois) for the SARS-CoV-2 IgG II Quant and 65

Abbott ARCHITECT SARS-CoV-2 IgM assays: both identified antibodies specific for the spike 66 protein. The SARS-CoV-2 IgG II Quant assay measured antibodies against the spike receptor 67 binding domain (RBD), the domain responsible for binding to ACE2 receptors and a major target 68 of neutralizing antibodies. 5 SARS-CoV-2 IgG II Quant assay results were reported in WHO 69 binding international units per milliliter (bIU/mL) by multiplying the arbitrary units per milliliter 70 (AU/mL) value by 0.142. 6 Past infection with SARS-CoV-2 was determined using the Abbott 71 ARCHITECT SARS-CoV-2 IgG assay that identified nucleocapsid-specific IgG. A lower cutoff 72 (≥0.4 S/CO) than the manufacturer's instructions was used for the SARS-CoV-2 nucleocapsid-73 specific IgG assay to increase sensitivity as described previously. 7 All samples in this study were 74 tested with all three assays. SARS-CoV-2 IgG II Quant and IgM assays were considered positive 75 according to the manufacturer's instructions (≥50 AU/mL and ≥ 1.0 S/CO, respectively). 76 77 A total of 71 AZD1222 vaccinated persons were assessed, 52.1% being males, with an average 78 age of 49.9 years ( Table 1 ). The average time between doses was 9.0 ± 0.8 weeks. Three weeks 79 after first dose all but one person was positive for SARS-CoV-2 RBD IgG and most persons with 80 longitudinal samples showed increased RBD IgG after the second AZD1222 dose that decreased 81 over time ( Figure 1A ). In participants without serological evidence of previous SARS-CoV-2 82 infection, median RBD IgG responses were 43.1 bIU/mL (303.5 AU/mL) after 3-7 weeks post 83 first dose, rising to 100.1 bIU/mL (704.6 AU/mL) 3-7 weeks post second dose, and falling to 84 46.9 bIU/mL (330.3 AU/mL) 16-22 weeks post second dose ( Figure 1B and Table 1 ). The only 85 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) greater RBD IgG levels after first dose than persons vaccinated without evidence of previous 91 SARS-CoV-2 infection (Supplemental Figure 1 ). The three greatest RBD IgG responses after 92 AZD1222 vaccination were from persons with SARS-CoV-2 PCR-confirmed infection within 2 93 months prior to receiving the first dose (Supplemental Table 1 For comparison to AZD1222 vaccination, the RBD IgG response was assessed with convalescent 105 sera from 21 unvaccinated SARS-CoV-2 PCR-confirmed persons, with 52.4% male, and an 106 average age of 54.1 years (Table 1) . RBD IgG responses were assessed 2-8 weeks after 107 symptoms onset (or positive PCR test for asymptomatic infections) for unvaccinated persons 108 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. ; https://doi.org/10. 1101 infected during the initial (April 2020-January 2021) and third waves (July 2021-September 109 2021) (Table 1 and Figure 1B ). Both waves were grouped together, as median RBD IgG 110 responses were not statistically different (Mann-Whitney test, p > 0.999) when comparing 111 severe-critical infections for the two waves (only severe-critical infection data was available for 112 the third wave). The median RBD IgG antibody response for unvaccinated PCR-confirmed 113 SARS-CoV-2 infected persons was 411.6 bIU/mL (2,898.9 AU/mL) when including all WHO 114 disease severities. Higher RBD IgG antibody levels were correlated with disease severity as 115 assessed by Spearman's correlation (ߩ = 0.44, p = 0.04), in agreement with previous 116 observations. 11 No correlation was identified for RBD IgG levels and age or sex for unvaccinated 117 SARS-CoV-2 infected persons as assessed by Spearman's correlation. 118 119 Most persons reported side effects and treatment after first AZD1222 dose, whereas after second 120 dose fewer persons reported side effects and they were of shorter duration (Table 2) This study provides the first assessment of the antibody response to AZD1222 vaccination in the 130

Caribbean region, and provides important information related to common side effects 131 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. We observed a lower RBD IgG response to AZD1222 than a previous study in the UK that 136 showed a median SARS-CoV-2 RBD IgG of 435 AU/mL for samples collected >21 days after 137 the first AZD1222 dose using the same Abbott SARS-CoV-2 IgG II Quant assay. 8 In our study 138 we showed a more modest median response of 303.5 AU/mL 3-7 weeks after the first AZD1222 139 dose that could possibly be explained by a younger age of the UK population examined and/or 140 genetic or other differences between populations. 141

The average time to second AZD1222 dose in this study was 9 weeks. The duration between 143 doses can affect the antibody response, with previous studies showing that receipt of the second 144 AZD1222 dose at 12 weeks resulted in greater antibody levels compared to boosting at 8 145 weeks. 13 More recent data showed that extended periods between first dose and second dose 146 greater >12 weeks is associated with higher antibody titers. 14 Although extended times from 147 initial dosing to second dose may be beneficial, consideration must be given for the extent of 148 SARS-CoV-2 circulation within populations that may favor shorter intervals between doses. 149 150 This study was limited by the modest sample size and neutralizing antibody testing that was not 151 done. While the SARS-CoV-2 IgG II Quant assay measures IgG antibodies against the spike 152 RBD, a key domain associated with neutralization, the assay does not directly measure 153 neutralizing antibodies. However, RBD IgG levels as measured with the Abbott SARS-CoV-2 154 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 IgG II Quant have previously been shown to be correlated with neutralizing antibodies, 15 and 155 recent studies show that RBD IgG antibody levels are associated with vaccine efficacy. 16,17 156 These studies examining correlates of protection indicate the potential utility of measuring RBD 157 IgG antibody levels in the broader population. Future assessment of a larger, nationally 158

representative Jamaican population with assessment of neutralizing antibodies would provide 159 more generalizable information and should be considered by public health officials. 160

In conclusion, our study shows that AZD1222 vaccination is associated with mild side effects in 162 the Jamaican population and almost always results in RBD IgG that is sustained for at least 22 163 weeks after vaccination, providing evidence-based support for the continued usage of AZD1222 164 in the English-speaking Caribbean. 165 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 25, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Figure 1 . SARS-CoV-2 RBD IgG antibody levels after AZD1222 vaccination and/or SARS-283

CoV-2 infection. SARS-CoV-2 RBD IgG was measured with the Abbott ARCHITECT SARS-284

CoV-2 IgG II Quant assay with results reported as arbitrary units per milliliter (AU/mL) on the 285 left y-axis and WHO binding international units per milliliter (bIU/mL) on the right y-axis. A) 286 Sera from all time points collected after AZD1222 vaccination was assessed for SARS-CoV-2 287 RBD IgG levels. The vertical dotted line indicates the average time of second AZD1222 dose. 288

All data points to the right of the vertical dotted were after second AZD1222 dose B) Sera was 289 collected from AZD1222 vaccinated persons 3-7 weeks after first and second dose, 16-22 weeks 290 after second dose, and for unvaccinated SARS-CoV-2 PCR-confirmed persons 2-8 weeks after 291 symptom onset (or PCR confirmation for asymptomatic persons). 292

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted October 25, 2021. ; https://doi.org/10.1101 https://doi.org/10. /2021 

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