Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease

Abstract

Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS‐CoV‐2 coronavirus. Measurement of those antibodies by neutralization or binding assays both have predictive value, with binding antibody titers giving the highest statistical correlation. However, the protective functions of antibodies are multiple. Antibodies with multiple functions other than neutralization influence efficacy. The role of cellular responses can be discerned with respect to CD4 + T cells and their augmentation of antibodies, and with respect to CD8 + cells with regard to control of viral replication, particularly in the presence of insufficient antibody. More information is needed on mucosal responses.

Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants

“…There is growing evidence that multiple mechanisms can contribute to protection from infection and severe disease, including humoral and cellular responses 26,[62][63][64][65] . In particular, antibody-dependent cell cytotoxicity (ADCC) and antibody-dependent opsonophagocytosis are Fc-mediated effector functions that can promote virus clearance and enhance adaptive immune responses in vivo, independently of direct viral neutralization.…”

“…SARS-CoV-2 S recognizes angiotensin-converting enzyme 2 (ACE2) as its main entry receptor, leading to membrane fusion and viral entry [17][18][19][20] . RBD-directed antibodies account for most neutralizing activity against vaccine-matched and vaccine-mismatched viruses, whereas the N-terminal domain is mostly targeted by variant-specific neutralizing antibodies [21][22][23][24][25][26][27][28][29][30][31][32][33][34] . Here, we set out to understand how the constellation of mutations in the BQ.1.1, XBB.1(.5) and BA.2.75.2 S variants affect the functional properties of SARS-CoV-2, humoral and memory immunity in humans, and recognition by therapeutic antibodies.…”

Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers

“…Our study demonstrates that serum nAb titers on the order of 1:30 are protective against symptomatic COVID-19 in both vaccination and monoclonal antibody prophylaxis settings. Although prior vaccine studies have consistently shown that spike protein–specific serum antibody concentrations are correlated with protection ( 2 , 3 , 8 ), the observed clinical efficacy conferred by adintrevimab against symptomatic Delta and Omicron BA.1/BA1.1 infection in SARS-CoV-2–naïve individuals provides strong evidence that nAbs are mechanistic in protection and that relatively high degrees of protection can be achieved at low serum nAb titers even in the absence of other forms of immunity such as T cell and memory B cell responses. However, the protective serum neutralization threshold defined here is not absolute, because breakthrough infections still occurred at time points associated with very high titers of serum nAb.…”

“…Studies in both humans and animal models have universally demonstrated that the induction of neutralizing antibody (nAb) responses correlates with protection against coronavirus disease 2019 (COVID-19) (2)(3)(4)(5)(6)(7)(8). However, the human CoP studies performed to date have been confounded by the presence of other forms of immunity induced by prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination (such as memory B cells and T cells).…”

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

“…Relatively little is known about infant-specific antibody responses to SARS-CoV-2, which could contribute to the age-dependent severity of coronavirus disease 2019 (COVID-19) (Chou et al, 2022; Pierce et al, 2020; Romero Starke et al, 2021). Plasma antibodies from individuals infected with SARS-CoV-2 target several viral proteins, though antibodies targeting the surface glycoprotein, Spike, are likely correlates of protection based on vaccine and SARS-CoV-2 challenge studies (reviewed in (Goldblatt et al, 2022)). Thus, characterizing the levels and functional capacity of antibodies that bind to Spike, and its subdomains, is important for understanding humoral immunity to SARS-CoV-2 across the age spectrum.…”