3.2.1. T cell-mediated responses
Progressive evidences proposed that both antibody and cell-mediated arms
of the adaptive immunity are the perquisites to defeat SARS-CoV2
infection (23). Meanwhile, the CD4+ T lymphocytes play
determinant roles in affordable antibody response and effective
CD8+ T cell cytotoxicity (24). Analysis of peripheral
blood T cell populations of recovered individuals from COVID-19
infection showed that all the patients had specific
CD4+ T helper (Th) cells for the SARS-CoV2 S protein,
while only 70% of blood samples contained the S protein specific
CD8+ cytotoxic T cells (16). Preclinical studies
indicated that the magnitude of specific T lymphocytes especially in the
lung is associated with better prophylaxis of COVID-19 patients (25).
Histopathological evidences proposed that respiratory mucosal
vaccination induced such lung resident memory T cell responses compare
to injectable vaccines and accompanied by reinforced defense against
SARS infection (26, 27). The phenotype of Th cells is also affected by
the vaccination route, so that severe lung manifestations ensuing
SARS-CoV infection were associated with Th2 phenotype dominance in
parenterally vaccinated individuals (28, 29), while switching to Th1
responses by mucosal vaccination led to less severe SARS infection (30).
So, inducing acceptable Th1 responses particularly in the tissue
resident T cell populations should be considered in COVID-19
vaccination. Altogether, it seems that priming T cell-mediated antiviral
responses is more reliable than induction of antibody secretion to
achieve effective immunization in the elderly, forcefully protect the
coverage of T cell response in designing the COVID-19 vaccine (23).
On the other hand, some evidences
showed that in 35% of healthy individuals with no history of SARS-CoV-2
infection, CD4+ T cells potentially recognized the
SARS-CoV2 spike protein. In addition,
CD4+ helper T
cells are able to identify other SARS-CoV2 proteins in 40 to 60% of
people not experience the COVID-19 infection [14, 15]. These
findings suggest that there is a cross-activity between
SARS-CoV2-specific
CD4+ T cells and
CD4+ T cells related to other members of human and
animal beta coronaviruses [16]. Therefore, in a society, there are
different degrees of pre-existing immunity that may explain the range of
susceptibility of individuals to COVID-19 infection. Surprisingly, the
cross-reactive CD4+ T cells primarily recognize the S2
subunit of the SARS-CoV2 spike protein. Also, CD4+ T
cells-derived from COVID-19 patients make vigorous cross-reactivity with
S2 domain of the human OC43 and 229E coronaviruses’ spike protein
[15]. Since cross-reactive T cells realize both structural and
non-structural viral epitopes [15, 17], it is likely that the
vastness of induced responses of such cross-reactive T-cells by
recombinant protein and viral vector-based vaccines compared to
multivalent COVID-19 vaccines are dissimilar. So, the efficacy of killed
or even live attenuated COVID-19 vaccine candidates possibly impaired
due to the presence of pre-existing cross-reactive immunity. So, in
terms of anti-coronavirus cross-reactive immunity, determining the
status of participants in clinical trials is imperative.