Robust Neutralizing Antibody Responses 6 Months Post Vaccination with BNT162b2: A Prospective Study in 308 Healthy Individuals

Elucidating long-term immunity following COVID-19 vaccination is essential for decision-making regarding booster shots. The aim of this study was to investigate the kinetics of neutralizing antibodies (Nabs) against SARS-CoV-2 up to six months after the second vaccination dose with the BNT162b2 mRNA vaccine. Nabs levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and 3 and 6 months after the second vaccination (NCT04743388). Three hundred and eight healthy individuals without malignant disease were included in this study. At six months, 2.59% of the participants had a Nabs value less than 30%, while 11.9% had Nabs values of less than 50%. Importantly, 58% of the subjects had Nabs values of more than 75%. Nabs were initially eliminated at a relatively slow rate, but after three months their elimination was 5.7 times higher. Older age was inversely associated with Nabs levels at all examined timepoints. Interestingly, a population modeling analysis estimated that half of the subjects will have Nabs values less than 73.8% and 64.6% at 9 and 12 months, respectively, post vaccination completion. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at six months following full vaccination with BNT162b2 in healthy individuals, which was more pronounced among older persons. These data may inform the public health policies regarding the prioritization of booster vaccine shots.

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Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

Cells ◽

10.3390/cells10081942 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1942

Author(s):

Evangelos Terpos ◽

Ioannis P. Trougakos ◽

Vangelis Karalis ◽

Ioannis Ntanasis-Stathopoulos ◽

Sentiljana Gumeni ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Health Workers ◽

Antibody Responses ◽

Healthy Individuals ◽

Younger Age ◽

Constant Rate ◽

Rate Of Decline ◽

A Prospective Study ◽

Kinetics Of ◽

Over Time

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.

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Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

Frontiers in Immunology ◽

10.3389/fimmu.2021.708523 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tiandan Xiang ◽

Boyun Liang ◽

Yaohui Fang ◽

Sihong Lu ◽

Sumeng Li ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Protein S ◽

Igg Antibodies ◽

Neutralizing Activity ◽

Specific Igg ◽

One Year ◽

Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

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The vaccinia-based Sementis Copenhagen Vector COVID-19 vaccine induces broad and durable cellular and humoral immune responses

10.1101/2021.09.06.459206 ◽

2021 ◽

Author(s):

Preethi Eldi ◽

Tamara H Cooper ◽

Natalie A Prow ◽

Liang Liu ◽

Gary K Heinemann ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

First Generation ◽

Neutralizing Antibody ◽

Immune Memory ◽

Antibody Activity ◽

Post Vaccination ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Heterologous Boost

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.

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TABUNGAN PERUMAHAN RAKYAT (TAPERA) DAN PENERAPANNYA DI DKI JAKARTA

Jurnal Muara Sains, Teknologi, Kedokteran dan Ilmu Kesehatan ◽

10.24912/jmstkik.v3i2.5630 ◽

2020 ◽

Vol 3 (2) ◽

pp. 321

Author(s):

Henriko Ganesha Putra ◽

Erwin Fahmi ◽

Kemal Taruc

Keyword(s):

Low Income ◽

Central Government ◽

Provincial Government ◽

Housing Finance ◽

Retirement Savings ◽

Important Lesson ◽

The Public ◽

Modeling Analysis ◽

The Republic

Occupancy is a basic need of every human being. As mandated by the 1945 Constitution, the State guarantees the fulfillment of citizens' needs for decent and affordable dwellings in the framework of developing Indonesian people who are wholly, self-conscious, independent and productive. The Public Housing Savings (Tapera) in accordance with Law of the Republic of Indonesia number 4 of 2016, is a long-term fund storage program that is used for housing finance, especially for Low-Income Communities (MBR). BAPERTARUM-PNS is an important lesson on how the goals of the housing savings are not utilized as retirement savings by most participants. The problem with this study is whether Tapera can be a solution for MBR in reaching funding for housing or repeating the failure of the BAPERTARUM-PNS program. Data collection from the Central Government, BP Tapera, and the Provincial Government of DKI Jakarta will be analyzed in the form of modeling of potential national and regional participation in and utilization of Tapera in DKI Jakarta Province. The results of the modeling analysis indicate a gap between Tapera's policies and people's expectations of a housing finance affordability solution for the MBR. AbstrakHunian merupakan kebutuhan dasar setiap manusia. Sebagaimana amanat UUD 1945, Negara menjamin pemenuhan kebutuhan warga negara atas tempat tinggal yang layak dan terjangkau dalam rangka membangun manusia Indonesia seutuhnya, berjati diri, mandiri, dan produktif. Tabungan Perumahan Rakyat (Tapera) sesuai Undang-Undang Republik Indonesia nomor 4 tahun 2016, merupakan program penyimpanan dana jangka panjang yang dimanfaatkan untuk pembiayaan perumahan, terutama bagi Masyarakat Berpenghasilan Rendah (MBR). BAPERTARUM-PNS menjadi pelajaran penting bagaimana ketidakberhasilan tujuan dari tabungan perumahan yang dimanfaatkan sebagai tabungan pensiun oleh sebagian besar peserta. Permasalahan dari studi ini adalah apakah Tapera dapat menjadi solusi bagi MBR dalam menjangkau pembiayaan untuk memperoleh hunian atau mengulangi ketidakberhasilan program BAPERTARUM-PNS. Pengumpulan data dari Pemerintah Pusat, BP Tapera, dan Pemerintah Provinsi DKI Jakarta akan dianalisis dalam bentuk Pemodelan potensi kepesertaan dan dana pemanfaatan Tapera secara nasional maupun regional di Provinsi DKI Jakarta. Hasil dari analisis pemodelan tersebut mengindikasikan adanya celah (gap) antara kebijakan Tapera dan harapan masyarakat akan hadirnya solusi keterjangkauan pembiayaan hunian bagi MBR.

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Tracking the polyclonal neutralizing antibody response to a dengue virus serotype 1 type-specific epitope across two populations in Asia and the Americas

Scientific Reports ◽

10.1038/s41598-019-52511-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Daniela V. Andrade ◽

Colin Warnes ◽

Ellen Young ◽

Leah C. Katzelnick ◽

Angel Balmaseda ◽

...

Keyword(s):

Dengue Virus ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Sri Lankan ◽

Human Monoclonal Antibodies ◽

Virus Serotype ◽

Serotype 1 ◽

Dengue Virus Serotypes ◽

Kinetics Of ◽

Two Populations

Abstract The four dengue virus serotypes (DENV1-4) cause major public health problems worldwide. Highly neutralizing type-specific human monoclonal antibodies (hmAbs) target conformation-dependent epitopes on the DENV envelope protein, including 1F4, a DENV1 type-specific hmAb. Using a recombinant DENV2 virus displaying the DENV1 1F4 epitope (rDENV2/1), we measured the proportion and kinetics of DENV1 neutralizing antibodies targeting the 1F4 epitope in individuals living in Asia and the Americas where different DENV1 genotypes were circulating. Samples from 20 individuals were analyzed 3 and 18 months post-primary DENV1 infection, alongside samples from 4 individuals collected annually for four years post-primary DENV1 infection, from two studies in Nicaragua. We also analyzed convalescent post-primary DENV1 plasma samples from Sri Lankan individuals. We found that neutralizing antibodies recognizing the 1F4 epitope vary in prevalence across both populations and were detected from 20 days to four years post-infection. Additionally, both populations displayed substantial variability, with a range of high to low proportions of DENV1 type-specific neutralizing antibodies recognizing the 1F4 epitope seen across individuals. Thus, the 1F4 epitope is a major but not exclusive target of type-specific neutralizing antibodies post-primary infection with different DENV1 genotypes in Asia and Latin America, and additional epitopes likely contribute to type-specific neutralization of DENV1.

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Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

Viruses ◽

10.3390/v13091844 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1844

Author(s):

Thomas P. Thomopoulos ◽

Margherita Rosati ◽

Evangelos Terpos ◽

Dimitris Stellas ◽

Xintao Hu ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Rna Binding ◽

Neutralizing Antibody ◽

Binding Domain ◽

High Morbidity ◽

Viral Loads ◽

Effective Treatment Modality ◽

Meta Analyses ◽

Humoral Responses ◽

Kinetics Of

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.

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Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA

Molecular Biomedicine ◽

10.1186/s43556-021-00054-z ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Yuan Liu ◽

Lianpan Dai ◽

Xiaoli Feng ◽

Ran Gao ◽

Nan Zhang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Protein Vaccine ◽

Humoral Immune ◽

Humoral Immune Responses ◽

The Face ◽

Potential Vaccine ◽

High Level

AbstractIn the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

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Vaccine-Associated Disease Enhancement (VADE): Considerations in Postvaccination COVID-19

Case Reports in Medicine ◽

10.1155/2021/9673453 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Rahajeng N. Tunjungputri ◽

Erpryta Nurdia Tetrasiwi ◽

Merlinda Veronica ◽

Jacub Pandelaki ◽

Fera Ibrahim ◽

...

Keyword(s):

Decision Making ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Vaccine Uptake ◽

The Public ◽

True Incidence ◽

Mass Immunization ◽

History Of ◽

New Phase

Introduction. The COVID-19 pandemic has entered a new phase with the roll-out of several vaccines worldwide at an accelerated phase. The occurrence of a more severe presentation of COVID-19 after vaccination may affect policymakers’ decision-making and vaccine uptake by the public. Vaccine-associated disease enhancement (VADE) is the modified presentation of infections in individuals after having received a prior vaccination. Currently, little is known about the potential of vaccine-associated disease enhancement (VADE) following COVID-19 immunization. Case Illustration. We herewith report two patients admitted with confirmed COVID-19 pneumonia with a history of CoronaVac vaccination. The first patient with a relatively milder course of the disease had received two doses of CoronaVac, whereas the second patient with a more progressive course of the disease received only one dose before developing symptoms and being admitted to the hospital. Our observations suggest that vaccination could act in boosting the inflammatory process and reveal the previously asymptomatic COVID-19 illness. Theoretically, vaccines could induce VADE, where only suboptimal, nonprotective titers of neutralizing antibodies were produced or proinflammatory T-helper type 2 response was induced. Secondly, enhanced respiratory disease (ERD) could manifest, where pulmonary symptoms are more severe due to peribronchial monocytic and eosinophilic infiltration. Understanding VADE is important for the decision-making by the public, clinicians, and policymakers and is warranted for successful vaccination uptake. Conclusion. We report two cases of patients developing COVID-19 shortly after CoronaVac vaccination in which VADE is likely. We recommend that current vaccination strategies consider the measurement of neutralizing antibody titer as a guide in ensuring the safest strategy for mass immunization. Studies are needed to investigate the true incidence of VADE on vaccinated individuals as well as on how to differentiate between VADE and severe manifestations of COVID-19 that are unrelated to vaccination.

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ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection

PLoS Pathogens ◽

10.1371/journal.ppat.1010046 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1010046

Author(s):

Dieter Mielke ◽

Gama Bandawe ◽

Jie Zheng ◽

Jennifer Jones ◽

Melissa-Rose Abrahams ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Immune Escape ◽

Viral Evolution ◽

Neutralizing Antibody ◽

Protective Role ◽

Viral Escape ◽

Immune Pressure ◽

Control Virus ◽

Kinetics Of ◽

Hiv 1

Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive approach to demonstrate the importance of this response. To enable us to deconvolute ADCC escape from neutralizing antibody (nAb) escape, we identified individuals soon after infection with detectable ADCC responses, but no nAb responses. We evaluated the kinetics of ADCC and nAb responses, and viral escape, in five recently HIV-1-infected individuals. In one individual we detected viruses that escaped from ADCC responses but were sensitive to nAbs. In the remaining four participants, we did not find evidence of viral evolution exclusively associated with ADCC-mediating non-neutralizing Abs (nnAbs). However, in all individuals escape from nAbs was rapid, occurred at very low titers, and in three of five cases we found evidence of viral escape before detectable nAb responses. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but that nAbs were far more effective. This suggests that if ADCC responses have a protective role, their impact is limited after systemic virus dissemination.

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Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers

Vaccines ◽

10.3390/vaccines9101092 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1092

Author(s):

Jean-Louis Bayart ◽

Jonathan Douxfils ◽

Constant Gillot ◽

Clara David ◽

François Mullier ◽

...

Keyword(s):

Half Life ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Healthcare Professionals ◽

Humoral Response ◽

Clinical Effectiveness ◽

Antibody Assay ◽

Post Vaccination ◽

Antibody Decline

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (−55.4% with total antibody assay; −89.6% with IgG assay) and seropositive individuals (−74.8% with total antibody assay; −79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13–65) in seronegative and 53 days (95% CI: 40–79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54–90) to 114 days (95% CI: 87–167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (−98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

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