Results
PSVN
ASYMPTOMATIC COVID-19, SARS-COV-2 INFECTION
For this study, we expanded testing of immune responses in the HIV-uninfected cohort enrolled in phase 2 and included 313 participants (128 placebo and 185 AZD1222 recipients). We do not report further on the kinetics of antibodies in the placebo group in this manuscript. After exclusions, 149 AZD1222 participants remained eligible in the final analysis, 99 of whom were anti-N seropositive before the first dose of AZD1222 and 58 of whom were seronegative and remained free of SARS-CoV-2 infection through to day 180 (Baseline characteristicsData are n (%) and median (IQR).p value comparing characteristics between baseline antiN IgG seropositive and baseline anti-N IgG seronegative individuals.Measured in safety cohort only.As expected, anti-S IgG GMCs (binding antibody units [BAU]/mL) at day 0 was higher in the seropositive (183·2; 95% CI 137·7–243·8) compared with the seronegative group (1·1; 0·8–1·5; p<0·0001), although only 37 (43%) of 87 of the seropositive group had antibody concentrations above PRRT for symptomatic wild-type–alpha COVID-19. At day 28, anti-S GMCs remained higher in the seropositive (2040·5; 1591·5–2616·3) compared with seronegative group (136·4; 102·2–182·0 BAU/mL), as was the percentage of individuals with anti-S IgG above the PRRT against wild-type–alpha (82 [92%] of 89 Between day 28 and day 42, there was no significant increase in anti-S IgG GMC in the seropositive group, but a 4·1 times increase in the seronegative group. Nevertheless, the day 42 anti-S IgG GMCs remained higher in the seropositive group (2194·9 [95% CI 1574·2–3060·2] Between day 42 and day 180, there was less of a decline in anti-S IgG GMC in the seropositive (73·5%; 95% CI 63·7–80·7%) compared with the seronegative group (84·7%; 77·9–89·4%); and anti-S IgG GMC remained higher in the seropositive group (517·8 [411·3–651·9] Antibody kinetics comparing AZD1222 vaccinated individuals who were anti-nucleocapsid IgG seropositive or seronegative at time of first dose of vaccine (A). Percentage of participants with anti-receptor binding domain IgG and anti-Spike IgG concentrations above the threshold for 80% risk reduction against wild-type or alpha variant of concern,* comparing AZD1222 vaccinated individuals who were anti-nucleocapsid IgG seropositive (anti-N IgGBAU=binding antibody units. Anti-N=anti-nucleocapsid. *The putative binding IgG threshold associated with 80% risk reduction of wild-type or alpha variant of concern symptomatic COVID-19 was as determined by Feng and colleagues;The dynamics of anti-RBD IgG and differences between the seropositive and seronegative groups were similar to that observed for anti-S IgG. Generally, the percentage of individuals with IgG greater than the PRRT against wild-type–alpha symptomatic COVID-19 was lower for anti-RBD IgG than anti-S IgG (The ADCC IgG GMT was higher in the seropositive group compared with the seronegative group at day 0 against D614G (499·9 [95% CI 362·5–683·9] Between day 28 and day 42, there was no further increase in ADCC IgG GMT in the seropositive group, compared with 2·3 and 2·7 times increase against D614G and the delta variant, respectively, in the seronegative group. Consequently, there was no difference in ADCC IgG GMT against D614G or delta between the seropositive compared with the seronegative group at day 42. Also, the ADCC IgG GMT at D180 did not differ by baseline sero status for either D614G or delta (PSVN GMTs against D614G were higher at days 28, 42, and 180 in the seropositive group compared with the seronegative group. Also, a higher percentage of the baseline seropositive group (23 [92%] of 25) than the seronegative group (three [27%] of 11; p<0·0002) had NAb above the PRRT against wild-type–alpha symptomatic COVID-19 at day 28. The GMTs against D614G increased 5·6 times between day 28 (81; 95% CI 28–237) and day 42 (451; 197–1035) in the seronegative group, whereas there was only a 1·3 times increase (1496; 768–2916 to 1933; 1283–2912) in the seropositive group. Nevertheless, GMT was 4·3 times higher in the seropositive group compared with the seronegative group at day 42; and the percentage with above the PRRT was higher in the seropositive group, albeit not significant (25 [100%] of 25] Pseudovirus neutralisation antibody activity to multiple variants 1 month after first AZD1222 dose (day 28), 14 days (day 42) and 142 days (day 180) the second dose of AZD1222, stratified by baseline anti-nucleocapsid IgG seropositive (anti-N IgGAnti-N=anti-nucleocapsid. *The putative pseudovirus neutralisation assay (PSVN) antibody titre of 185 associated with 80% risk reduction of wild-type or alpha variant of concern symptomatic COVID-19 was as determined by Feng and colleagues.The NAb GMT against D614G was 1·5 to 12·8 times higher than against the beta VOC at the different time points. At day 28, 19 (76%) of 25 of the seropositive compared with none of the seronegative group had NAb above the PRRT against beta symptomatic COVID-19. There was only a modest increase factor in NAb against beta between day 28 and day 42 in the seropositive (1·5) and seronegative (2·2) groups. The day 180 NAb GMT against beta in the seropositive group (178; 95% CI 96–329) was 5·1 times higher than the peak at day 42 in the seronegative group (35; 23–55). The percentage of individuals with NAb titres greater than the PRRT against beta symptomatic COVID-19 was consistently higher in the seropositive group than the seronegative group at days 28 and 42 (19 [76%] of 25] The NAb kinetics against A.VOI.V2, gamma and SARS-CoV between the seropositive and seronegative group, as well as percentage at each timepoint above the PRRT threshold, were similar to that observed for beta VOC (The NAb GMT against D614G was 2·1 to 7·4 times higher than against delta at the different timepoints. Against delta variant, there was no significant increase in NAb GMTs after the second dose of AZD1222 (between days 28 and 42) in the baseline seropositive or seronegative group, however, GMT remained higher in the seropositive group (416; 95% CI 294–588 The NAb GMT against D614G was 3·0 to 27·4 times higher than against omicron BA.1. At day 28, the NAb GMT against BA.1 was higher in the seropositive group (499; 95% CI 282–885) than the seronegative group (14; 9–22). There was no increase in NAb against BA.1 in either the seropositive group or seronegative group following the second dose of AZD1222, and NAb GMTs remained higher in the seropositive group at day 42 (535; 290–988 Kinetics of NAbs against omicron BA.4 mirrored omicron BA.1. NAb GMTs against BA.4 were higher in the seropositive group compared with the seronegative group at all timepoints. For the seropositive group, NAb GMTs decreased over time, whereas NAb GMTs ranged from 13 (95% CI 9–19) to 16 (9–27) between day 28 and day 180 in the seronegative group. The percentage of individuals with NAb above the PRRT against BA.4 symptomatic COVID-19 was 21 (88%) of 24 at day 28 and day 42 in the seropositive group, and 0% in the seronegative group. At day 180, no participants had a titre above the putative threshold and there was a 90·4% (80·9–95·2) decrease in the NAb GMT from day 42 in the seropositive group.