1158. Immunogenicity of COVID-19 vaccine four-dose series in healthy community dwelling adults 50 years and above: interim analysis from the ‘PRospEctiVe EvaluatioN of immuniTy after COVID-19 vaccines’ (PREVENT-COVID) study

BACKGROUND: Adults aged > 50 years are at increased risk for severe coronavirus disease 2019 (COVID-19). This study evaluated immunogenicity of COVID-19 vaccines in healthy adults aged > 50 years through quantification of antigen specific antibody concentration and function post-vaccination with two, three and four COVID-19 vaccine doses. METHODS: Eighty-four immunocompetent, community-dwelling adults 50 to 83 years old (median age 61 years) were enrolled. We measured index virus spike protein (S) specific antibody responses to mRNA (mRNA-1273 or BNT162b2) and/or ChAdOx1-S COVID-19 vaccines. Participants were separated into three groups: (1) mRNA/mRNA/mRNA/mRNA; (2) ChAdOx1-S/mRNA/mRNA; (3) ChAdOx1-S/ChAdOx1-S/mRNA. Responses were quantified via: anti-S IgG geometric mean concentrations (GMCs) (binding antibody units [BAU]/mL), total relative IgG avidity index (TRAI) (avidity units, AU) collected up to one, four, and seven-months after each dose. One-way ANOVA, Tukey-Kramer post-hoc compared groups and Welch’s t-test compared timepoints. RESULTS: At one month post-dose two, mRNA/mRNA (1137 BAU/mL, p = 0.0003) and ChAdOx1-S/mRNA (1388, p < 0.0001) had higher anti-S IgG GMCs compared with ChAdOx1-S/ChadOx1-S (195 BAU/mL). However, TRAI was similar amongst the three groups (all p > 0.05); mRNA/mRNA (70 AU), ChAdOx1-S/mRNA (66 AU) and ChAdOx1-S/ChAdOx1-S (58 AU). S-IgG GMCs at one month post-dose three were higher for mRNA/mRNA/mRNA than ChAdOx1-S/ChAdOx1-S/mRNA (1316 vs. 569 BAU/mL p = 0.0162). Similar to post-dose two, post-dose three there were no significant differences in TRAI between groups (all p > 0.05); mRNA/mRNA/mRNA (95 AU), ChAdOx1-S/mRNA/mRNA (98 AU), ChAdOx1-S/ChAdOx1-S/mRNA (101 AU). For mRNA/mRNA/mRNA participants, a fourth mRNA vaccine dose increased S-IgG GMCs at one-month post-dose four compared with one month post-dose two (2825 vs. 1137 BAU/mL, p = 0.0126) and maintained TRAI between timepoints (71 vs. 70 AU, p = 0.9877). CONCLUSION: mRNA vaccines are more immunogenic compared to ChAdOx1-S with regards to S-specific antibody concentration. mRNA boosters maintained antibody avidity. Together, TRAI and anti-S IgG GMCs should be further evaluated when recommending additional booster doses and considered when determining protection against COVID-19. DISCLOSURES: Sofia R. Bartlett, PhD, Abbvie: Advisor/Consultant|Abbvie: Grant/Research Support|Cepheid: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support