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.