Superior magnitude and durability of hybrid immunity following SARS-CoV-2 infection

Paskorn Sritipsukho,^1,2 Sira Nanthapisal,^1,3 Boonchu Sirichongkolthong,¹ Pakatip Sinlapamongkolkul,¹ Peera Jaru-Ampornpan,^3,4 Orawan Himananto,⁴ Kirana Yoohat,⁴ Jaraspim Narkpuk,⁴ Thorntun Deangphare⁴

Affiliations:
¹ Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
² Center of Excellence in Applied Epidemiology, Thammasat University, Pathum Thani, Thailand
³ Infectious and Immunology Research Group, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
⁴ National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand

Abstract

Background: The emergence of the SARS-CoV-2 Delta variant necessitated examining hybrid immunity (vaccination-plus-infection) to optimize boosting strategies. We analyzed the kinetics, magnitude, and durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) following Delta infection.
Objective: This study analyzed the kinetics, magnitude, and long-term durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) levels following Delta variant infection across individuals with diverse vaccination histories.
Methods: This observational cohort study monitored 161 patients with varying vaccination histories for up to 16 weeks post-infection. Responses were compared against SARS-CoV-2 naïve controls receiving a two-dose inactivated series plus a heterologous booster. Sub-analyses assessed post-infection booster immunogenicity.
Results: Prior vaccination significantly enhanced humoral responses. Patients with two prior doses achieved the highest median Anti-sRBD IgG peaks, surpassing vaccine-boosted naïve controls. While unvaccinated individuals exhibited delayed primary responses, hybrid immunity demonstrated superior durability with slower antibody decay than vaccine-only immunity. Crucially, while a post-infection booster effectively primed unvaccinated patients, early boosting in previously vaccinated individuals yielded minimal immunological gain.
Conclusions: Hybrid immunity confers superior antibody magnitude and durability, highlighting the synergy between vaccination and natural infection. Early post-infection boosting in previously vaccinated individuals appears to provide limited additional benefit, supporting tailored booster timing strategies.