Anti-SARS-CoV-2 antibody dynamics after primary vaccination with two-dose inactivated whole-virus vaccine, heterologous mRNA-1273 vaccine booster, and Omicron breakthrough infection in Indonesian health care workers
Authors: Suwarti Suwarti , Lazarus Gilbert , Zanjabila Sabighoh , Sinto Robert , Fransiska Fransiska , Deborah Theresia , Oktavia Dwi , Junaidah Junaidah , Santayana Santayana , Surendra Henry , Yuliana Jeng , Pardosi Herlina , Nuraeni Nunung , Soebianto Saraswati , Susilowati Novi Dwi , Subekti Decy , Pradipta Ariel , Baird J. Kevin , Tan Le Van , Dunachie Susanna , Shankar Anuraj H. , Nelwan Erni J. , Hamers Raph L. ,   SEACOVARIANTS Consortium, Anh Nguyen To , Hong Nguyen Thi Thu , Truc Truong Hoang Chau , Ny Nguyen Thi Han , Han Do Duong Kim , Thanh Le Kim , Nguyet Lam Anh , Thuy Cao Thu , Nhu Le Nguyen Truc , Thanh Tran Tan , Yen Lam Minh , Hang Vu Thi Ty , Kieu Pham Tieu , Hoang Vo Tan , Thao Nguyen Thi , Chambers Mary , Thanh Vu Duy , Hoang Tran Chieu , Thwaites C. Louise , Thwaites Guy , van Doorn H. Rogier , Tung Trinh Son , Mongkolsapaya Juthathip , Screaton Gavin , Dijokaite-Guraliuc Aiete , Das Raksha , Liu Chang , Supasa Piyada , Selvaraj Muneeswaran , Dunachie Susanna J. , Klenerman Paul , Jones E. Yvonne , Stuart David I. , Kronsteiner-Dobramysl Barbara , Zewdie Martha , Abraham Priyanka , Hill Jennifer , Tayipto Yanie , Paramita Isana , Lin-Fa Wang , Wah Tan Chee , Chee Yap Wee , Lee Lim Beng , Suwarti  , Simarmata Eva , Dien Ragil , Dejnirattisai Wanwisa , Chantima Warangkana , Chantratita Narisara , Poolchanuan Prapassorn , Tiacharoen Vichapon , Dulsuk Adul , Iamsirithaworn Sophon , Day Nick , Cheah Phaik Yeong , Poomchaichote Tassawan , Boonthaworn Kanpong , Ngoc Nghiem My , Grifoni Alba , Sette Alessandro 
Published: August 2024

Abstract
Background
Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter.

Methods
We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI.

Results
Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI.

Conclusions
mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.