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(searched for: doi:10.1038/s41591-021-01432-4)
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, Jim K. Yee, Ashley Sukhu, Yuqing Qiu, Sophie Rand, Paul D. Barone, Ying Hao, , Qing H. Meng, Fred S. Apple, et al.
Abstract:
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under “real-world” conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaïveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaïveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaïveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ~6-months post-D1 (p=0.002). Although NaïveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaïveVax did reach similar avidity by ~6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.
, Hala Alshammary, Gagandeep Singh, Ariel Raskin, Fatima Amanat, Angela Amoako, , Adriana van de Guchte, PARIS study group, Komal Srivastava, et al.
Published: 20 October 2021
Abstract:
Background Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring. Methods We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions. Findings We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible. Interpretation Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity. Funding This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.
Amandine Le Bourgeois, Marianne Coste‐Burel, , , Alice Garnier, Berthe‐Marie Imbert, Thomas Drumel, Beatrice Mahé, Viviane Dubruille, Nicolas Blin, et al.
Published: 20 October 2021
British Journal of Haematology; https://doi.org/10.1111/bjh.17911

Zheng Quan Toh, Jeremy Anderson, Nadia Mazarakis, Melanie Neeland, Rachel A. Higgins, Karin Rautenbacher, Kate Dohle, Jill Nguyen, Isabella Overmars, Celeste Donato, et al.
Published: 18 October 2021
Abstract:
Importance The immune response in children with SARS-CoV-2 infection is not well understood. Objective To compare seroconversion in children and adults with non-hospitalized (mild) SARS-CoV-2 infection and to understand the factors that influence this. Design Participants were part of a household cohort study of SARS-CoV-2 infection. Weekly nasopharyngeal/throat swabs and blood samples were collected during the acute and convalescent period following PCR diagnosis for analysis. Setting Participants were recruited at the Royal Children’s Hospital, Melbourne, Australia between May and October 2020. Participants Those who had a SARS-CoV-2 PCR-positive nasal/throat swab. Main outcomes and measures SARS-CoV-2 antibody and cellular responses in children and adults. Seroconversion was defined by seropositivity in all three serological assays. Results Among 108 SARS-CoV-2 PCR-positive participants, 57 were children (median age: 4, IQR 2-10) and 51 were adults (median age: 37, IQR 34-45). Using three established serological assays, a lower proportion of children seroconverted compared with adults [20/54 (37.0%) vs 32/42 (76.2%); (p<0.001)]. This was not related to viral load, which was similar in children and adults [mean Ct 28.58 (SD: 6.83) vs 24.14 (SD: 8.47)]. Age and sex also did not influence seroconversion or the magnitude of antibody response within children or adults. Notably, in adults (but not children) symptomatic adults had three-fold higher antibody levels than asymptomatic adults (median 227.5 IU/mL, IQR 133.7-521.6 vs median 75.3 IU/mL, IQR 36.9-113.6). Evidence of cellular immunity was observed in adults who seroconverted but not in children who seroconverted. Conclusion and Relevance In this non-hospitalized cohort with mild COVID-19, children were less likely to seroconvert than adults despite similar viral loads. This has implications for future protection following COVID-19 infection in children and for interpretation of serosurveys that involve children. Further research to understand why children are less likely to seroconvert and develop symptoms following SARS-CoV-2 infection, and comparison with vaccine responses may be of clinical and scientific importance. Key points Question What proportion of children with non-hospitalized (mild) SARS-CoV-2 infection seroconvert compared to adults? Findings In this cohort study conducted in 2020, we found the proportion of children who seroconverted to SARS-CoV-2 was half that in adults despite similar viral load. Meaning Serology is a less reliable marker of prior SARS-CoV-2 infection in children. SARS-CoV-2-infected children who do not seroconvert may be susceptible to reinfection. Our findings support strategies to protect children against COVID-19 including vaccination.
, Maria E. Montez-Rath, Jialin Han, Pablo Garcia, LinaCel Cadden, Patti Hunsader, Curt Morgan, Russell Kerschmann, Paul Beyer, Mary Dittrich, et al.
Published: 14 October 2021
Abstract:
Background Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies. Methods Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination. Results Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively). Conclusions The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.
Jeremy Baldwin, Sakshi Piplani, Isaac G Sakala, , Lei Li,
Published: 14 October 2021
Abstract:
Vaccines are key in charting a path out of the COVID-19 pandemic. However, development of new vaccines is highly dependent on availability of analytical methods for their design and evaluation. This paper highlights the challenges presented in having to rapidly develop vaccine analytical tools during an ongoing pandemic, including the need to address progressive virus mutation and adaptation which can render initial assays unreliable or redundant. It also discusses the potential of new computational modeling techniques to model and analyze key viral proteins and their attributes to assist vaccine production and assay design. It then reviews the current range of analytical tools available for COVID-19 vaccine application, ranging from in vitro assays for immunogen characterization to assays to measure vaccine responses in vivo. Finally, it provides a future perspective for COVID-19 vaccine analytical tools and attempts to predict how the field might evolve over the next 5–10 years.
, Sibylle C. Mellinghoff
Published: 6 October 2021
The publisher has not yet granted permission to display this abstract.
Published: 29 September 2021
by MDPI
Abstract:
Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.
Yihao Liu, Qin Zeng, Caiguanxi Deng, Mengyuan Li, Liubing Li, Dayue Liu, Jie Mei, Ruohui Mo, Qian Zhou, Min Liu, et al.
Published: 15 September 2021
Abstract:
SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccine and the potential need for a third booster dose for the HCWs. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 31.2 AU/ml to 9.2 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 66.8 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly “no responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which has implications for future booster strategies that the frontline HCWs, individuals with low serological response to 2 dose of vaccine and immune compromised patients could benefit from a third dose of inactivated vaccine.
, Patrick Mucher, , Astrid Radakovics, Manuela Repl, , , Johannes W Bigenzahn, Florentina Leitner, , et al.
Published: 5 September 2021
Abstract:
Objectives Various commercial anti-Spike SARS-CoV-2 antibody tests are used for studies and in clinical settings after vaccination. An international standard for SARS-CoV-2 antibodies has been established to achieve comparability of such tests, allowing conversions to BAU/ml. This study aimed to investigate the comparability of antibody tests regarding the timing of blood collection after vaccination. Methods For this prospective observational study, antibody levels of 50 participants with homologous AZD1222 vaccination were evaluated at 3 and 11 weeks after the first dose and 3 weeks after the second dose using two commercial anti-Spike binding antibody assays (Roche and Abbott) and a surrogate neutralization assay. Results The correlation between Roche and Abbott changed significantly depending on the time point studied. Although 3 weeks after the first dose, Abbott provided values three times higher than Roche, 11 weeks after the first dose, the values for Roche were twice as high as for Abbott, and 3 weeks after the second dose even 5-6 times higher. Conclusions The comparability of quantitative anti-Spike SARS-CoV-2 antibody tests is highly dependent on the timing of blood collection after vaccination. Therefore, standardization of the timing of blood collection might be necessary for the comparability of different quantitative SARS-COV-2 antibody assays. Abstract Figure
, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, Tal Patalon
Published: 25 August 2021
Abstract:
Background Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
María M. Gonzalez Lopez Ledesma, Lautaro Sanchez, Diego S. Ojeda, Santiago Oviedo Rouco, Andres H. Rossi, Augusto Varese, Ignacio Mazzitelli, Carla A. Pascuale, Esteban A. Miglietta, Pamela E. Rodríguez, et al.
Published: 25 August 2021
Abstract:
Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we observed a similar process after Sputnik V vaccination. We examined the longitudinal antibody responses and viral neutralizing capacity to variants of concern (VOCs: Alpha, Beta, Gamma, and Delta) and a broadly spread variant of interest (VOI: Lambda) in volunteers up to 6 months after receiving the Sputnik V vaccine in Argentina. A collection of 1,800 serum samples obtained between January and August 2021 was used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing potency to the first-wave linages of SARS-CoV-2 and VOC increases within four months of vaccination, suggesting that antibody maturation occurs. This increase was more evident for the Beta and Gamma variants, which showed the highest propensity for neutralization escape. Our observations suggest that protection increases over the six months following vaccination as a consequence of antibody maturation, resulting in improved potency of antibodies to viral escape mutations.
Daniel Junker, Alex Dulovic, Matthias Becker, Teresa R. Wagner, Philipp D. Kaiser, Bjoern Traenkle, Ulrich Rothbauer, Katharina Kienzle, Stefanie Bunk, Carlotta Strümper, et al.
Published: 22 August 2021
Abstract:
As global vaccination campaigns against SARS-CoV-2 proceed, there is emerging interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. To assess neutralizing capacity, we developed a bead-based multiplex ACE2 RBD competition assay as a large scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and RBD, this assay detects the presence of Nabs against SARS-CoV2 in serum. Using this multiplex approach allows the simultaneous analysis of Nabs against all SARS-CoV-2 variants of concern and variants of interest in a single well. Following validation, we analyzed 325 serum samples from 186 COVID-19 patients of varying severity. Neutralization capacity was reduced for all variants examined compared to wild-type, especially for those displaying the E484K mutation. The neutralizing immune response itself, while highly individualistic, positively correlates with IgG levels. Neutralization capacity also correlated with disease severity up to WHO grade 7, after which it reduced.
Eva Schrezenmeier, Hector Rincon-Arevalo, Ana-Luisa Stefanski, Alexander Potekhin, Henriette Staub-Hohenbleicher, Mira Choi, Friederike Bachmann, Vanessa Pross, Charlotte Hammett, Hubert Schrezenmeier, et al.
Published: 12 August 2021
Abstract:
Background Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need. Significance statement Protection of solid organ transplant recipients against SARS-Cov-2 by vaccination remains an unmet need given the low immunogenicity of available vaccines in the presence of immunosuppression. Administration of a third dose to 25 kidney transplant recipients (KTR) resulted in seroconversion in 36% of patients, associated with significant quantitative and functional changes within the spike-antigen-specific B-cell- and CD4+ T-helper cell compartment. Our data support the need for individual humoral monitoring of immunosuppressed individuals after vaccination as well as continued efforts to adapt vaccination protocols for this at-risk group.
M. Verónica López, Sabrina E. Vinzón, Eduardo G. A. Cafferata, Felipe J. Nuñez, Ariadna Soto, Maximiliano Sanchez-Lamas, Jimena Afonso, Diana Aguilar-Cortes, Gregorio D. Ríos, Juliana T. Maricato, et al.
Published: 11 August 2021
Abstract:
Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric hAdV5 vector. The vaccine (named CoroVaxG.3) is based on three pillars: i) high expression of Spike to enhance its immunodominance by using a potent promoter and a mRNA stabilizer; ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; iii) use of Spike stabilized in a prefusion conformation. Transduction with CoroVaxG.3 expressing Spike (D614G) dramatically enhanced Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3 vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha) and P.1 (gamma) Spikes, as well as an authentic WT and P.1 SARS-CoV-2 isolates. Neutralizing antibodies did not wane even after 5 months making this kind of vaccine a likely candidate to enter clinical trials
Sabrina E. Racine-Brzostek, Jim Yee, Ashley Sukhu, Yuqing Qiu, Sophie Rand, Paul Barone, Ying Hao, He S. Yang, Qing H Meng, Fred S Apple, et al.
Published: 5 August 2021
Abstract:
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under “real-world” conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaïveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaïveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaïveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ∼6-months post-D1 (p=0.002). Although NaïveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaïveVax did reach similar avidity by ∼6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.
Juan Manuel Carreño, Hala Alshammary, Gagandeep Singh, Ariel Raskin, Fatima Amanat, Angela Amoako, Ana Silvia Gonzalez-Reiche, Adriana van de Guchte, Mahmoud Awawda, Radhika Banu, et al.
Published: 23 July 2021
Abstract:
Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed.1 However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning.2 Several of these viral variants have the potential to partially escape neutralizing antibody responses warranting continued immune-monitoring. Here, we tested a number of currently circulating viral variants of concern/interest, including B.1.526 (Iota), B.1.1.7+E484K (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and C.37 (Lambda) in neutralization assays using a panel of post-mRNA vaccination sera. The assays were performed with authentic SARS-CoV-2 clinical isolates in an assay that mimics physiological conditions. We found only small decreases in neutralization against B.1.526 and an intermediate phenotype for B.617.2. The reduction was stronger against a sub-variant of C.37, followed by B.1.351 and B.1.1.7+E484K. C.37 is currently circulating in parts of Latin America3 and was detected in Germany, the US and Israel. Of note, reduction in a binding assay that also included P.1, B.1.617.1 (Kappa) and A.23.1 was negligible. Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.
, Robyn M. Stuart, Katherine Rosenfeld, , Michael White, Cliff C. Kerr, Daniel J. Klein, Michael Famulare
Published: 1 June 2021
Abstract:
The functional relationship between neutralizing antibodies (NAbs) and protection against SARS-CoV-2 infection and disease remains unclear. We jointly estimated protection against infection and disease progression following natural infection and vaccination from meta-study data. We find that NAbs are strongly correlated with prevention of infection and that any history of NAbs will stimulate immune memory to moderate disease progression. We also find that natural infection provides stronger protection than vaccination for the same level of NAbs, noting that infection itself, unlike vaccination, carries risk of morbidity and mortality, and that our most potent vaccines induce much higher NAb levels than natural infection. These results suggest that while sterilizing immunity may decay, we expect protection against severe disease to be robust over time and in the face of immune-evading variants.
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