Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection

Keon Young Lee; Kyoung-Ho Song; Kyoung Hwa Lee; Jin Yang Baek; Eu Suk Kim; Young Goo Song; Yong Chan Kim; Yoon Soo Park; Jin Young Ahn; Jun Yong Choi; Won Suk Choi; Seongman Bae; Shin-Woo Kim; Ki Tae Kwon; Eun-Suk Kang; Kyong Ran Peck; Sung-Han Kim; Hye Won Jeong; Jae-Hoon Ko

doi:10.1016/j.vaccine.2024.05.003

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection

Vaccine. 2024 May 9:S0264-410X(24)00539-5. doi: 10.1016/j.vaccine.2024.05.003. Online ahead of print.

Authors

Keon Young Lee¹, Kyoung-Ho Song², Kyoung Hwa Lee³, Jin Yang Baek⁴, Eu Suk Kim², Young Goo Song³, Yong Chan Kim⁵, Yoon Soo Park⁵, Jin Young Ahn⁶, Jun Yong Choi⁶, Won Suk Choi⁷, Seongman Bae⁸, Shin-Woo Kim⁹, Ki Tae Kwon¹⁰, Eun-Suk Kang¹¹, Kyong Ran Peck¹, Sung-Han Kim¹², Hye Won Jeong¹³, Jae-Hoon Ko¹⁴

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
² Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
³ Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁴ Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Asia Pacific Foundation for Infectious Diseases (APFID), Seoul, Republic of Korea.
⁵ Division of Infectious Diseases, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea.
⁶ Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁷ Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea.
⁸ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁹ Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
¹⁰ Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
¹¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
¹² Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: shkimmd@amc.seoul.kr.
¹³ Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea. Electronic address: hwjeong@chungbuk.ac.kr.
¹⁴ Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: jaehoon.ko@samsung.com.

PMID: 38729909
DOI: 10.1016/j.vaccine.2024.05.003

Abstract

Introduction: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear.

Methods: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike₁) and beta and gamma variant (Spike₂) were utilized.

Results: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike₁ and Spike₂ proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike₂ response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05).

Conclusion: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Keywords: Breakthrough infection; COVID-19; Cytokine; Interferon-gamma releasing assay; SARS-CoV-2; Vaccine.