SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

Abstract

With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic

“…Taken together, this evidence supports our finding of poor concordance between the spike RDB IgG and the assay targeting the nucleocapsid, with far fewer asymptomatic infections detected using the anti-nucleocapsid assay than the in-house anti-spike RBD assay. After vaccination, however, assays based on spike antigen are unsuitable for detecting SARS-CoV-2 infection [ 9 ]. Hence, there is an urgent need for developing more sensitive and robust methods based on a non-spike antigen to detect individuals who experienced asymptomatic or mild infection to control community spread.…”

“…In addition, two in-house Enzyme-Linked Immunosorbent Assays (ELISA) based on the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the SARS-CoV-2 spike protein were performed as previously described [ 9 , 10 ]. The sensitivity and specificity of the test were 98% and 100%, respectively, nine days after symptom onset in patients with confirmed SARS-CoV-2 infection.…”

SARS-CoV-2 Seroprevalence: Demographic and Behavioral Factors Associated With Seropositivity Among College Students in a University Setting

“…Blood samples were received at UNC-CH between 11/18/2020 and 01/19/2021 where they underwent anti-SARS-CoV-2 Spike antibody testing. The serology assay is based on spike RBD antigen and measures total Ig (IgG, IgA and IgM) with an estimated sensitivity of 95% and specificity of 96% 23 , 24 . Serology test results were categorized as positive, negative, indeterminate, or non-viable (due to poor sample quality).…”

A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic

“…In addition, two in-house Enzyme-Linked Immunosorbent Assays (ELISA) based on the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the SARS-CoV-2 spike protein were performed as previously described [9, 10]. The sensitivity and specificity of the test were 98% and 100%, respectively, 9 days after symptom onset in patients with confirmed SARS-CoV-2 infection.…”