Serum Neutralizing Activity Research Articles

Receptor binding domain-IgG levels correlate with protection in residents facing SARS-CoV-2 B.1.1.7 outbreaks.

BackgroundLimited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS‐CoV‐2 and severe COVID‐19, and its association with post‐vaccine humoral response.Methods396 residents from seven NHs suffering a SARS‐CoV‐2 B.1.1.7 (VOC‐α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS‐CoV‐2 real‐time reverse‐transcriptase polymerase chain reaction on nasopharyngeal swab test (RT‐qPCR). SARS‐CoV‐2 receptor‐binding domain (RBD) of the S1 subunit (RBD‐IgG) was measured in all residents. Nucleocapsid antigenemia (N‐Ag) was measured in RT‐qPCR‐positive residents and serum neutralizing antibodies in vaccinated residents from one NH.ResultsThe incidence of positive RT‐qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non‐vaccinated residents (21/48; 43.7%; p < .01). COVID‐19–induced deaths were observed in 5 of the 48 non‐vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non‐vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD‐IgG (n = 325) were associated with a lower SARS‐CoV‐2 incidence. No in vitro serum neutralization activity was found for RBD‐IgG levels below 1050 AU/ml. RBD‐IgG levels were inversely associated with N‐Ag levels, found as a risk factor of severe COVID‐19.ConclusionsTwo BNT162b2 doses are associated with a 48% reduction of SARS‐CoV‐2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC‐α outbreak. Post‐vaccine RBD‐IgG levels correlate with BNT162b2 protection against SARS‐CoV‐2 B.1.1.7.

Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine

ObjectiveThe dynamic adaptive immune responses elicited by the inactivated virus vaccine CoronaVac remain elusive. MethodsIn a prospective cohort of 100 healthcare professionals naïve for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received two doses of CoronaVac, we analysed SARS-CoV-2-specific humoral and cellular responses at four different timepoints, including before vaccination (T1), 2 weeks after the first dose (T2), 2 weeks after the booster dose (T3), and 8–10 weeks after the booster dose (T4). SARS-CoV-2-specific antibodies, serum neutralizing activities, peripheral B cells, CD4+ and CD8+ T cells and their memory subsets were simultaneously measured in this cohort. ResultsSARS-CoV-2 spike-specific IgG responses reached a peak (geometric mean titre (GMT) 54827, 30969–97065) after two doses and rapidly declined (GMT 502, 212–1190) at T4, whereas suboptimal IgA responses were detected (GMT 5, 2–9). Spike-specific circulating B cells (0.60%, 0.46–0.73% of total B cells) and memory B cells (1.18%, 0.92–1.44% of total memory B cells) were effectively induced at T3 and sustained over time (0.33%, 0.23–0.43%; 0.87%, 0.05–1.67%, respectively). SARS-CoV-2-specific circulating CD4+ T cells (0.57%, 0.47–0.66%) and CD8+ T cells (1.29%, 1.04–1.54%) were detected at T3. At T4, 0.78% (0.43–1.20%) of memory CD4+ T cells and 0.68% (0.29–1.30%) of memory CD8+ T cells were identified as SARS-CoV-2-specific, while 0.62% (0.51–0.75%) of CD4+ T cells and 0.47% (0.38–0.58%) of CD8+ T cells were SARS-CoV-2-specific terminally differentiated effector memory cells. Furthermore, age and interval between doses affected the magnitude of CoronaVac-induced immune responses. SARS-CoV-2 memory CD4+ T cells were strongly associated with both receptor binding domain (RBD)-specific memory B cells (r 0.87, p <0.0001) and SARS-CoV-2-specific memory CD8+ T cells (r 0.48, p <0.0001). ConclusionsCoronaVac induced robust circulating and memory B cell and T cell responses. Our study offers new insight into the underlying immunobiology of inactivated virus vaccines in humans and may have implications for vaccine strategies in the future.

Serum neutralizing activity against SARS-CoV-2 variants in hospitalized COVID-19 patients

BackgroundThe recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact on immune protection elicited by natural infection or conferred by vaccination. This study aimed at evaluating the neutralizing activity against the viral variants emerged in the United Kingdom (B.1.1.7), Brazil (B.1.1.28.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020.MethodsSerum samples of 42 COVID-19 patients hospitalized in Italy between March and May 2020, were included in the present study. Samples available for each patient at three time points were selected: hospital admission sample, sample showing the highest neutralizing antibody titre against 2019-nCov/Italy-INMI1 strain (Wuhan strain), and the last sample available during hospital stay. Samples were tested for SARS-CoV-2 neutralizing antibody against B.1.1.7, B.1.1.28.1, and B.1.351 wild type viruses by micro-neutralization assay.ResultsThe decrease of neutralizing antibody titre for all three variants was statistically significant at any time point. At discharge/decease, 59.5% of patients showed a decrease (≥2 fold) in neutralizing antibody titre against the B.1.1.7 variant, 83.3% against the B.1.1.28.1 variant, and 90.5% against the B.1.351 variant with respect to the original strain.ConclusionsThe reduction of neutralizing antibody titres against all analysed variants, and in particular B.1.1.28.1 and B.1.351 ones, suggests that previous symptomatic infection might be not fully protective to exposure of SARS-CoV-2 variants carrying a set of relevant spike mutations.Key messages A reduction in neutralizing antibody titres against B.1.1.7, B.1.351, and B.1.1.28.1 variants was observed.Previous symptomatic infection might be not fully protective to exposure of SARS-CoV-2 variants carrying a set of relevant spike mutations.

Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity

Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1-4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.

Weak Cross-Lineage Neutralization by Anti SARS-CoV-2 Spike Antibodies after Natural Infection or Vaccination Is Rescued by Repeated Immunological Stimulation.

After over one year of evolution, through billions of infections in humans, SARS-CoV-2 has evolved into a score of slightly divergent lineages. A few different amino acids in the spike proteins of these lineages can hamper both natural immunity against reinfection, and vaccine efficacy. In this study, the in vitro neutralizing potency of sera from convalescent COVID-19 patients and vaccinated subjects was analyzed against six different SARS-CoV-2 lineages, including the latest B.1.617.2 (or Delta variant), in order to assess the cross-neutralization by anti-spike antibodies. After both single dose vaccination, or natural infection, the neutralizing activity was low and fully effective only against the original lineage, while a double dose or a single dose of vaccine, even one year after natural infection, boosted the cross-neutralizing activity against different lineages. Neither binding, nor the neutralizing activity of sera after vaccination, could predict vaccine failure, underlining the need for additional immunological markers. This study points at the importance of the anamnestic response and repeated vaccine stimulations to elicit a reasonable cross-lineage neutralizing antibody response.

A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children.

BackgroundMost children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown.MethodsWe analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods.FindingsFifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines.InterpretationA weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize pediatric severe COVID-19. Because comorbidities are highly prevalent in children with severe COVID-19, further studies are needed to clarify their contribution in the weak antibody response observed in severe disease.FundingNational Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548).

Оценка клинического течения COVID-19 у пациентов, вакцинированных «Спутник V», изменчивости RBD-домена S-белка SARS-CoV-2 и вируснейтрализующих свойств сыворотки

The COVID-19-associated mortality remains high. Studying the features of the COVID-19 course in vaccinated patients, who have got ill on different dates after vaccination, compared to unvaccinated individuals is relevant. The study was aimed to assess clinical and immunological features of the COVID-19 course, as well as to assess humoral immunity (virus neutralizing activity, VNA) and SARS-CoV-2 S protein RBD domain variation in the groups of patients, previously vaccinated with Sputnik V, and unvaccinated patients. A total of 251 patients with confirmed diagnosis of COVID-19 were enrolled, of them 116 individuals were previously vaccinated with one or two Sputnik V vaccine components, and 135 patients were not vaccinated (comparison group). Individuals over 50 years of age prevailed (82.8%). The patients, who received two vaccine components, had mild to moderate COVID-19 (92.1%). In the group of unvaccinated patients, 11 individuals received treatment in the ICU, 10 of them died. The viral load was significantly lower in vaccinated patients. Mutations of SARS-CoV-2, such as S477N, S477N+A522S, E484K and E484K+S494P, were identified both in vaccinated and unvaccinated patients. Assessment of the neutralizing activity of sera revealed no significant differences in VNA against different variants of SARS-CoV-2 mutations. The data obtained demonstrate that the lack of vaccination is an aggravating factor and is capable of increasing the risk of severe course and death in patients with COVID-19.

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.

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients—despite a decline in total S-specific antibodies—neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that—compared with mRNA vaccination—natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

Intranasal vaccination with a recombinant protein CTA1-DD-RBF protects mice against hRSV infection

Human respiratory syncytial virus (hRSV) infection is a major pediatric health concern worldwide. Despite more than half a century of efforts, there is still no commercially available vaccine. In this study, we constructed and purified the recombinant protein CTA1-DD-RBF composed of a CTA1-DD mucosal adjuvant and prefusion F protein (RBF) using Escherichia coli BL21 cells. We studied the immunogenicity of CTA1-DD-RBF in mice. Intranasal immunization with CTA1-DD-RBF stimulated hRSV F-specific IgG1, IgG2a, sIgA, and neutralizing antibodies as well as T cell immunity without inducing lung immunopathology upon hRSV challenge. Moreover, the protective immunity of CTA1-DD-RBF was superior to that of the RBF protein, as confirmed by the assessment of serum-neutralizing activity and viral clearance after challenge. Compared to formalin-inactivated hRSV (FI-RSV), intranasal immunization with CTA1-DD-RBF induced a Th1 immune response. In summary, intranasal immunization with CTA1-DD-RBF is safe and effective in mice. Therefore, CTA1-DD-RBF represents a potential mucosal vaccine candidate for the prevention of human infection with hRSV.

Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines

Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

ObjectiveTo assess the antibody response in non-immunocompromised adults after two doses of BNT162b2. MethodsProspective, single-centre observational study in non-immunocompromised adults aged 18 years or more who received two doses of BNT162b2. The study contemplates analyses of serum samples collected 1.5, 3, 6, 9 and 12 months after the second dose of BNT162b2; results of the 1.5- and 3-month time-points are presented in this report. Antibodies against the receptor binding domain of the S1 subunit of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (anti-RBD antibodies) were measured using a commercial quantitative immunoassay. A threshold of 4160 AU/mL (corresponding to an ID50 of 1:250) was used as surrogate marker for serum neutralizing activity. ResultsOf 273 hospital workers who received two doses of BNT162b2, 260 (95%) agreed to participate in the study; 2/260 (0.8%) were excluded because of immunocompromised conditions. At the time of this report, 230/258 (89%) participants (mean age 46.0 years (SD 11.4 years); 143/230 (62%) female; 87/230 (38%) male) had completed 3 months of follow up after the second dose of BNT162b2. Thirty-six (16%) of the 230 had documented mild SARS-CoV-2 infection before receiving the first dose of BNT162b2. Median (interquartile range (IQR)) anti-RBD titres 1.5 months after vaccination were 9356 (5844–16 876) AU/mL; 3 months after vaccination, median anti-RBD titres had declined to 3952 (2190–8561) AU/mL (p < 0.001). Of 199/230 (86.5%) participants who had anti-RBD titres above 4160 AU/mL 1.5 months after the second dose of BNT162b2, only 95/230 (41%) maintained anti-RBD titres above this level 3 months after vaccination (p < 0.001). ConclusionsThe decline of anti-RBD antibodies 3 months after the second dose of BNT162b2 is of concern because it raises the possibility of a short-lived humoral immunity after vaccination. Booster doses of BNT162b2 might be required to maintain high titres of anti-RBD antibodies over time.

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus-neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate that children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.

The rapid adaptation of SARS-CoV-2-rise of the variants: transmission and resistance.

The causative factor of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously mutating. Interestingly, identified mutations mainly occur in the spike (S) protein which interacts with the ACE2 receptor and is cleaved via serine protease TMPRSS2. Some mutated strains are becoming dominant in various parts of the globe because of increased transmissibility as well as cell entry efficacy. Remarkably, the neutralizing activity of monoclonal antibodies, convalescent sera, and vaccines against the variants has been reported to be significantly reduced. Therefore, the efficacy of various monoclonal antibodies therapy and vaccines against these variants is becoming a great global concern. We herein summarize the current status of SARS-CoV-2 with gears shifted towards the recent and most common genetic variants in relation to transmission, neutralizing activity, and vaccine efficacy.

Development of a microneutralization assay for HSV-2

BackgroundPlaque Reduction Neutralization Test (PRNT) is the standard assay used for measuring neutralizing antibody responses to Herpes simplex virus type-2 (HSV-2). The PRNT is a cumbersome, time-consuming and laborious assay. The development of a faster, high throughput microneutralization assay (MNA) for HSV-2 viruses carried out in a 96-well format will allow for rapid testing of large numbers of samples for drug and vaccine development. MethodsWe describe the generation of a MNA that utilizes a pair of anti-HSV human monoclonal antibodies (mAbs) for virus detection in HSV-2 infected Vero cells. Antibodies were generated by B-cell cloning from PBMC’s isolated from HSV-1 negative/HSV-2 positive donors. We describe the selection and characterization of the antibodies used for virus detection by ELISA with purified, recombinant anti-HSV glycoproteins, antibody binding in infected cells, and Western Blot. We determine the anti-HSV-2 neutralizing titers of immune sera from mice by MNA and PRNT and compare these results by linear regression analysis. ResultsWe show that neutralization titers for HSV-2, determined by the 96-well MNA correlate with titers determined by a PRNT completed in 24-well plates in both the absence (R2 = 0.8250) and presence (R2 = 0.7075) of complement. ConclusionsWe have successfully developed an MNA that can be used in place of the burdensome PRNT to determine anti-HSV-2 neutralizing activity in serum. This MNA has much greater throughput than the PRNT, allowing many more samples to be processed in a shorter time saving ∼90 % of the time required by the laboratory scientist to complete the task as compared to the traditional PRNT.

Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan.

BackgroundAs of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established.MethodsWe investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients’ sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses.ResultsMost sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants.ConclusionsThe cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.

Lack of neutralizing activity in nonconvalescent sera, regardless of ABO blood group and anti-A isoagglutinin titer

BackgroundSeveral ABO blood groups have been associated with the likelihood of infection, severity, and/or outcome of COVID-19 in hospitalized cohorts, raising the hypothesis that anti-A isoagglutinins in non-A-group recipients could act as neutralizing antibodies against SARS-CoV-2.Materials and methodsWe run live virus neutralization tests using sera from 58 SARS-CoV-2 seronegative blood donors (27 O-group and 31 A-group) negatives for SARS-CoV-2 IgG to investigate what degree of neutralizing activity could be detected in their sera and eventual correlation with anti-A isoagglutinin titers.ResultsWe could not find clinically relevant neutralizing activity in any blood group, regardless of anti-isoagglutinin titer,DiscussionOur findings suggest that mechanisms other than neutralization explain the differences in outcomes from COVID19 seen in different ABO blood groups.

Walking down the memory lane with SARS-CoV-2 B cells.

The B-cell response to COVID-19 vaccines in convalescent individuals.

The SARS-CoV-2 spike L452R-E484Q variant in the Indian B.1.617 strain showed significant reduction in the neutralization activity of immune sera.

To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1 (dominant variant identified in the current India outbreak) on the infectivity and neutralization activities of the immune sera, L452R and E484Q (L452R-E484Q variant), pseudotyped virus was constructed (with the D614G background). The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay. Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G. However, there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain (RBD) protein, convalescent patients, and healthy vaccinees vaccinated with an mRNA vaccine. In addition, there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of the immune sera from vaccinated non-human primates. These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2. Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/new vaccine development.

Cross-neutralization of SARS-CoV-2 B.1.1.7 and P.1 variants in vaccinated, convalescent and P.1 infected

ObjectivesThe emergence of new variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) around the world significantly complicated the exit from Coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to evaluate the serum neutralizing activity of three cohorts. MethodsBNT162b2-elicited serum (N = 103), candidates as hyper-immune plasma donors (N = 90) and patients infected with the SARS-CoV-2 P1 variant (N = 22) were enrolled. Three strains of SARS-CoV-2 have been tested: 20A.EU1, B.1.1.7 (alpha) and P.1 (gamma). Neutralizing antibodies (NT-Abs) titers against SARS-CoV-2 were evaluated. ResultsB.1.1.7 and P.1 are less efficiently neutralized by convalescent wild-type infected serums if compared to 20A.EU1 strain (mean titer 1.6 and 6.7-fold lower respectively). BNT162b2 vaccine-elicited human sera show an equivalent neutralization potency on the B.1.1.7 but it is significantly lower for the P.1 variant (mean titer 3.3-fold lower). Convalescent P.1 patients are less protected from other SARS-CoV-2 strains with an important reduction of neutralizing antibodies against 20A.EU1 and B.1.1.7, about 12.2 and 10.9-fold, respectively. ConclusionsBNT162b2 vaccine confers immunity against all the tested VOCs, while previous SARS-CoV-2 infection may be less protective.

Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection

More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.