Introduction
The coronavirus disease 2019 (COVID-19) pandemic has been wreaking havoc for nearly three years, with more than 758 million infected cases worldwide as of March 2023 (https://covid19.who.int/). The herd immunity raised by the vaccination or natural infection has been recognized as the barrier to cut off the transmission of the virus. Thus, the immune memory characteristics of the convalescents and the vaccinees, including cellular and humoral immunity have raised wide concern.1-3 Cellular immune memory can last up to 1 year after the COVID-19 patient’s recovery,2,3 while for humoral immunity, neutralizing antibodies (NAb) are still detectable 16 months after symptoms onset, but the neutralizing activity of antibodies has marked declined over time.4 But the immune statuses of convalescents become complicated in consideration of the application of vaccines.
In the past three years, to effectively prevent COVID-19 and achieve herd immunity with minimal loss of life, different types of vaccines have been developed and widely used globally, such as mRNA, inactivated, polypeptide subunit, and adenovirus vector vaccine.5-8It was indicated that S-RBD IgG, NAb, and CD4+ T cell responses waned quickly after a single inactivated vaccine dose, and further increased after the second dose. Virus-specific CD4+ T cell responses generated by two doses of vaccination lasted more than 2 months.7A significantly reduced neutralizing activity against Omicron was observed in the convalescent and two-dose BBIBP-CorV vaccination group, which was elevated by a third homologous inactivated vaccine booster.9 Studies also showed that the Omicron breakthrough infected individuals immunized with inactivated vaccines maintained high level of neutralization against wild type (WT) and variants, and the enhancement effects by breakthrough infection were of significant differences between 2-dose and 3-dose groups.10Prior immunization with inactivated prototype strain vaccines substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery after virus breakthrough.11 However, the features of the humoral and cellular immune memory are still largely unknown, especially among COVID-19 convalescents in the first wave during the pandemic who later received two or three doses of inactivated vaccines.
The emergence of different severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, notably Delta and Omicron, has led to successive waves of pandemics, posing enormous public health challenges.12 Studies showed that Omicron is more transmissible than other variants.13-16 The Omicron variant harbors 32 mutations in spike glycoproteins,17raising concern about the Omicron escaping from immunity established by WT infection or vaccination. Studies have shown that sera from COVID-19 convalescents or individuals who were vaccinated exhibited substantially diminished neutralizing activity against Omicron.18-23It has been reported that mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373 vaccines elicit highly conserved cellular immunity to Omicron.24-28 The memory status of T-cell immunity and the cross-reactivity to Omicron among inactivated vaccines were still unexplored, especially in terms of the vaccines recovered from COVID-19.
In this study involving COVID-19 and control cohorts, we assessed the antibody and T-cell responses to WT and Omicron strains in COVID-19 convalescents who have later inoculated with inactivated vaccines, and healthy individuals after routine two- or three-dose vaccination. This study will expand knowledge of the immune features and the memory persistence in vaccinated COVID-19 convalescents.