Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS-CoV-2 Spike protein after natural infection or COVID-19 vaccination

Abstract

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

Long-Term Kinetics of SARS-CoV-2 Antibodies and Impact of Inactivated Vaccine on SARS-CoV-2 Antibodies Based on a COVID-19 Patients Cohort

“…A previous study found that RBD-IgG persisted in 96.8% (31 of 32) of subjects at 14 months (21), which was slightly higher than 89.31% (284/318) at 15.6 months after symptom onset in our study. We also found that vaccinated individuals had higher antibody levels of IgG, RBD-IgG, S-IgG, N-IgG and neutralizing antibodies than unvaccinated individuals, consistent with the conclusions reached by Carlos et al (22).…”

Assessment of COVID-19 vaccination effectiveness

“…Pokazuje jednak, że metody oceny, kto jest ozdrowieńcem albo u kogo miano przeciwciał chroni przed chorobą, mają wady. Liczy się funkcja tych przeciwciał, a nie tylko ich stężenie [7]; podobnie jak liczba nawet uśpionych producentów przeciwciał (limfocytów B, które ich tymczasowo nie uwalniają), ich repertuar i zdolność do szybkiej reakcji -mobilizacji. Takiej oceny nie daje się dokonać w czasie testów przesiewowych powszechnie stosowanych do wykrycia przeciwciał.…”

Immunogenesis in patients with medium and severe coronavirus infection – dynamics in different age groups

“…The overall kinetics of the antibody response to SARS-CoV-2 is similar to that of SARS-CoV-1, characterized by expressed seroconversion (IgM / IgG) 7-14 days after the onset of symptoms and antibody concentrations persisting weeks to tens of months after infection (Henry et al 2020), A prospective study evaluating the kinetics of glycoprotein-specific antibodies in patients with COV-ID-19 found that IgA antibodies were produced early (in the first week) and peak at day 20-22, while IgM antibodies reached high titers at 10-12 th day, which subsequently decreases, usually 18 days after the onset of symptom (Sariol et al 2021). Our results show that at the end of the third month after illness, IgM titers tend to zero.…”

“…The aim was to evaluate the response of human antibodies to SARS-CoV-2 in 149 individuals recovering from COV-ID-19 of varying severity. Plasma neutralization of SARS-CoV-2 pseudovirus by convalescent patients with COV-ID-19 infection collected on average 39 days after the onset of symptoms has variable half-maximal neutralizing titers (NT50) (Sariol et al 2021). It should be noted that these are conclusions made on the basis of analysis of results obtained from in vitro laboratory methods.…”

“…SARS-CoV-2-specific CD4 + T cells and CD8 + T cells decrease with a half-life of 3-5 months. A number of studies have shown that B-cell, CD4 + T-cell and CD8 + T-cell populations, as separate components of SARS-CoV-2 immune memory, show different kinetics (Sariol et al 2021).…”