scholarly journals Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant

2021 ◽  
Author(s):  
Venkata-Viswanadh Edara ◽  
Lilin Lai ◽  
Malaya Sahoo ◽  
Katharine Floyd ◽  
Mamdouh Sibai ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Live Virus ◽  
Global Pandemic ◽  
Virus Assay ◽  
Recent Emergence ◽  
The World ◽  
Antibody Resistance ◽  
Second Wave

SARS-CoV-2 has caused a devastating global pandemic. The recent emergence of SARS-CoV-2 variants that are less sensitive to neutralization by convalescent sera or vaccine-induced neutralizing antibody responses has raised concerns. A second wave of SARS-CoV-2 infections in India is leading to the expansion of SARS-CoV-2 variants. The B.1.617.1 variant has rapidly spread throughout India and to several countries throughout the world. In this study, using a live virus assay, we describe the neutralizing antibody response to the B.1.617.1 variant in serum from infected and vaccinated individuals. We found that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. This suggests that protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. As the B.1.617.1 variant continues to evolve, it will be important to monitor how additional mutations within the spike impact antibody resistance, viral transmission and vaccine efficacy.

scholarly journals Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant

2021 ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Katharine Floyd ◽  
Lilin Lai ◽  
Meredith Gardner ◽  
William Hudson ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Live Virus ◽  
Virus Neutralization Assay ◽  
Recent Emergence ◽  
The Uk ◽  
Induced Immunity

AbstractAntibody responses against the SARS-CoV-2 Spike protein correlate with protection against COVID-19. Serum neutralizing antibodies appear early after symptom onset following SARS-CoV-2 infection and can last for several months. Similarly, the messenger RNA vaccine, mRNA-1273, generates serum neutralizing antibodies that are detected through at least day 119. However, the recent emergence of the B.1.1.7 variant has raised significant concerns about the breadth of these neutralizing antibody responses. In this study, we used a live virus neutralization assay to compare the neutralization potency of sera from infected and vaccinated individuals against a panel of SARS-CoV-2 variants, including SARS-CoV-2 B.1.1.7. We found that both infection- and vaccine-induced antibodies were effective at neutralizing the SARS-CoV-2 B.1.1.7 variant. These findings support the notion that in the context of the UK variant, vaccine-induced immunity can provide protection against COVID-19. As additional SARS-CoV-2 viral variants continue to emerge, it is crucial to monitor their impact on neutralizing antibody responses following infection and vaccination.

scholarly journals An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Martijn A. Langereis ◽  
Irina C. Albulescu ◽  
Judith Stammen-Vogelzangs ◽  
Morindy Lambregts ◽  
Ken Stachura ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Animal Species ◽  
Close Contact ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Venezuelan Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
Replicon Particle ◽  
Nasal Swabs ◽  
Animal Hosts

AbstractEarly in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

scholarly journals Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

2020 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Linda J. Rennick ◽  
Sham Nambulli ◽  
Lindsey R. Robinson-McCarthy ◽  
William G. Bain ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Rna Viruses ◽  
Rapid Evolution ◽  
Neutralizing Antibody ◽  
Antigenic Drift ◽  
Human Populations ◽  
Spike Glycoprotein ◽  
Evolutionary Pattern ◽  
Antigenic Sites ◽  
Global Pandemic

AbstractZoonotic pandemics follow the spillover of animal viruses into highly susceptible human populations. Often, pandemics wane, becoming endemic pathogens. Sustained circulation requires evasion of protective immunity elicited by previous infections. The emergence of SARS-CoV-2 has initiated a global pandemic. Since coronaviruses have a lower substitution rate than other RNA viruses this gave hope that spike glycoprotein is an antigenically stable vaccine target. However, we describe an evolutionary pattern of recurrent deletions at four antigenic sites in the spike glycoprotein. Deletions abolish binding of a reported neutralizing antibody. Circulating SARS-CoV-2 variants are continually exploring genetic and antigenic space via deletion in individual patients and at global scales. In viruses where substitutions are relatively infrequent, deletions represent a mechanism to drive rapid evolution, potentially promoting antigenic drift.

scholarly journals EMERGENCE OF SECOND WAVE OF SARS-COV-2 INFECTIONS DURING THE ONGOING COVID-19 PANDEMIC: A MINI REVIEW

2020 ◽  
Vol 8 (Spl-1-SARS-CoV-2) ◽  
pp. S57-S65
Author(s):  
Bhumika Prajapati ◽  
◽  
Kranti Suresh Vora ◽  
Zareena Fathah ◽  
Ranjit Sah ◽  
...  
Keyword(s):  
Epidemic Curve ◽  
Exponential Increase ◽  
Global Pandemic ◽  
The World ◽  
Type 3 ◽  
Second Wave ◽  
Vulnerable Elderly ◽  
Future Plans

The COVID-19 outbreak originated from Wuhan, China has spread over the world, causing a “Global Pandemic”. We analyzed daily confirmed cases and deaths from different countries to understand the progression of the ongoing pandemic in different parts around the world. The data indicated that the pandemic is in different stages in different countries, where they are either at the end of the second wave or middle or early phase of it or still in the middle of the first wave of infection, and they can be divided into four groups. Type 1 countries such as UK, France, Spain, and the Netherlands are currently witnessing the second wave of infection with an exponential increase in daily cases. Countries such as Australia, United States, Japan, and Poland are currently in the declining stage of second-wave, grouped as Type 2 countries. Type 3 countries such as Germany, Italy, Belgium, and Russia are recently seeing the second wave with slowly rising of confirmed cases. Type 4 countries including India, Brazil, Argentina, and Mexico are currently fighting against the first wave of COVID-19. These countries have a chance to learn from the countries which have overcome the second wave successfully. To be ahead of the epidemic curve and preventing it, countries need to make future plans on family, hospital, and community levels. Isolation of the highly vulnerable elderly people and young children, preventing social or public gathering, following the guidelines of COVID-19 prevention including wearing face masks regularly can save countries from devastating effects of the second wave of pandemic COVID-19.

scholarly journals Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant

2021 ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Carson Norwood ◽  
Katharine Floyd ◽  
Lilin Lai ◽  
Meredith E. Davis-Gardner ◽  
...  
Keyword(s):  
South African ◽  
Receptor Binding ◽  
Symptom Onset ◽  
Protective Immunity ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Live Virus ◽  
Fold Reduction ◽  
Antibody Titers

SUMMARYThe emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies to neutralize these variants. We compared antibody binding and live virus neutralization of sera from naturally infected and spike mRNA vaccinated individuals against a circulating SARS-CoV-2 B.1 variant and the emerging B.1.351 variant. In acutely-infected (5-19 days post-symptom onset), convalescent COVID-19 individuals (through 8 months post-symptom onset) and mRNA-1273 vaccinated individuals (day 14 post-second dose), we observed an average 4.3-fold reduction in antibody titers to the B.1.351-derived receptor binding domain of the spike protein and an average 3.5-fold reduction in neutralizing antibody titers to the SARS-CoV-2 B.1.351 variant as compared to the B.1 variant (spike D614G). However, most acute and convalescent sera from infected and all vaccinated individuals neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective immunity is retained against COVID-19.

scholarly journals Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xin Xu ◽  
Sheng Nie ◽  
Yanqun Wang ◽  
Quanxin Long ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Half Time ◽  
Peak Titer ◽  
Neutralization Rate ◽  
Repeat Infection ◽  
Post Onset

AbstractOur understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC50 titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49–80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86–130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.

scholarly journals 564. SARS-CoV-2 Ferritin Nanoparticle Vaccines Elicit Broad SARS Coronavirus Immunogenicity

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
M G Joyce ◽  
Wei-Hung Chen ◽  
Rajeshwer Sankhala ◽  
Agnes Hajduczki ◽  
Paul Thomas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibody ◽  
High Dose ◽  
Pandemic Preparedness ◽  
Virus Stock ◽  
Global Pandemic ◽  
Recent Emergence ◽  
Blocking Activity ◽  
Antibody Levels ◽  
Antigenic Profile

Abstract Background The zoonotic emergence of SARS-CoV-2 quickly developed into a global pandemic. Multiple vaccine platforms have been advanced to clinical trials and emergency use authorization. The recent emergence of SARS-CoV-2 virus variants with Spike receptor-binding domain (RBD) and N-terminal domain (NTD) mutations, highlights the need for next-generation vaccines that can elicit immune responses that are resilient against Spike mutations. Methods Using a structure-based vaccine design approach, we developed multiple optimized SARS-CoV-2 nanoparticle immunogens that recapitulate the structural and antigenic profile of the SARS-CoV-2 prefusion spike. We assessed these immunogens in murine immunogenicity studies and in a K18-hACE2 transgenic mouse model with a SARS-CoV-2 challenge. Immune sera from vaccinated mice were assessed for SARS-CoV-2 binding, and neutralization against SARS-CoV-2, variants of concern, and the heterologous SARS-CoV-1 virus. Results In combination with a liposomal-saponin based adjuvant (ALFQ), these immunogens induced robust binding, ACE2-inhibition, and authentic virus and pseudovirus neutralization. A Spike-Ferritin nanoparticle (SpFN) vaccine elicited neutralizing ID50 titers >10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values >10,000 values after two immunizations. Purified antibody from SpFN- or RFN-immunized mice was transfused into K18-ACE2 transgenic mice and challenged with a high-dose SARS-CoV-2 virus stock. In order to understand the breadth of vaccine-elicited antibody responses, we analyzed SpFN- and RBD-FN-immunized animal sera against a set of heterologous SARS-CoV-2 RBD variants and SARS-CoV RBD. High binding titers with ACE2-blocking activity were observed against SARS-CoV-2 variants and the heterologous SARS-CoV-1 RBD. Furthermore, both SpFN- and RFN-immunized animal sera showed SARS-CoV-1 neutralizing ID50 titers of >2000. Conclusion These observations highlight the importance of SARS-CoV-2 neutralizing antibody levels in providing protection against emerging SARS-like coronaviruses and provide a robust platform for pandemic preparedness. Structure-based design enables development of a SARS-CoV-2 nanoparticle immunogen. Disclosures All Authors: No reported disclosures

scholarly journals COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian He ◽  
Qunying Mao ◽  
Jialu Zhang ◽  
Lianlian Bian ◽  
Fan Gao ◽  
...  
Keyword(s):  
Safety Data ◽  
Current Understanding ◽  
Effective Vaccine ◽  
Clinical Testing ◽  
Vaccination Programs ◽  
Vaccine Candidates ◽  
Global Pandemic ◽  
The World ◽  
Human Use ◽  
Second Wave

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.

scholarly journals A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma

2021 ◽  
pp. eabi8452
Author(s):  
Craig Fenwick ◽  
Priscilla Turelli ◽  
Céline Pellaton ◽  
Alex Farina ◽  
Jérémy Campos ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralizing Antibodies ◽  
Competitive Inhibition ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Serum Samples ◽  
Live Virus ◽  
Protein Variants

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that, although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the β (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.

scholarly journals Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

2021 ◽  
Author(s):  
Bennett J Davenport ◽  
Alexis Catala ◽  
Stuart M Weston ◽  
Robert M Johnson ◽  
Jeremy Ardunay ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Live Virus ◽  
Physiochemical Properties ◽  
Multivalent Display ◽  
Specific Igg ◽  
Coronavirus Infection ◽  
Rapid Generation ◽  
One Year ◽  
Antibody Levels

The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the U.S. within one year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a designer nanoparticle platform using phage-like particles (PLPs) derived from bacteriophage lambda for multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD-SARS-PLPs, RBD-MERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD-SARS- or RBD-MERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose response studies, immunization with as little as one microgram of RBD-SARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD-SARS-PLPs, RBD-MERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.

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