Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days

BackgroundA vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.ObjectivesTo evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.MethodsWe determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.ResultsThe seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (>31 years) (P<0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P<0.05).ConclusionsAntibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.

Download Full-text

Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

Science ◽

10.1126/science.abd7728 ◽

2020 ◽

Vol 370 (6521) ◽

pp. 1227-1230 ◽

Cited By ~ 59

Author(s):

Ania Wajnberg ◽

Fatima Amanat ◽

Adolfo Firpo ◽

Deena R. Altman ◽

Mark J. Bailey ◽

...

Keyword(s):

New York ◽

New York City ◽

Severe Acute Respiratory Syndrome ◽

Antibody Response ◽

York City ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Spike Protein ◽

Global Pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Download Full-text

SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Nature Communications ◽

10.1038/s41467-021-23942-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nanda Kishore Routhu ◽

Narayanaiah Cheedarla ◽

Venkata Satish Bollimpelli ◽

Sailaja Gangadhara ◽

Venkata Viswanadh Edara ◽

...

Keyword(s):

Antibody Response ◽

Antibody Titer ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Neutralizing Antibody ◽

Significant Loss ◽

Lung Pathology ◽

Live Virus ◽

Suitable Candidate ◽

Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

Download Full-text

A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

Journal of General Virology ◽

10.1099/vir.0.80844-0 ◽

2005 ◽

Vol 86 (5) ◽

pp. 1435-1440 ◽

Cited By ~ 65

Author(s):

Milosz Faber ◽

Elaine W. Lamirande ◽

Anjeanette Roberts ◽

Amy B. Rice ◽

Hilary Koprowski ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Protein S ◽

S Protein ◽

Cellular Immune Responses ◽

Glycoprotein G ◽

Cellular Immune ◽

Animal Reservoirs ◽

S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

Download Full-text

Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation

Journal of Virology ◽

10.1128/jvi.02437-16 ◽

2017 ◽

Vol 91 (13) ◽

Cited By ~ 18

Author(s):

Normand Blais ◽

Martin Gagné ◽

Yoshitomo Hamuro ◽

Patrick Rheault ◽

Martine Boyer ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Antibody Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Human Respiratory Syncytial Virus ◽

Vaccine Antigen ◽

Significant Advance ◽

F Protein ◽

Syncytial Virus

ABSTRACT The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

Download Full-text

Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.603228 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tybbysay P. Salinas ◽

Jose L. Garrido ◽

Jacqueline R. Salazar ◽

Publio Gonzalez ◽

Nicole Zambrano ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Serum Levels ◽

Mortality Rates ◽

Antibody Responses ◽

Cytokine Profiles ◽

Th2 Cytokine ◽

Igg1 Subclass ◽

Asymptomatic Individuals

BackgroundNew World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.MethodsFor this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.ResultsHigh titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.ConclusionA Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.

Download Full-text

Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients

10.21203/rs.3.rs-1073046/v1 ◽

2021 ◽

Author(s):

Jira Chansaenroj ◽

Ritthideach Yorsaeng ◽

Nasamon Wanlapakorn ◽

Chintana Chirathaworn ◽

Natthinee Sudhinaraset ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Symptom Onset ◽

Neutralizing Antibodies ◽

Serum Antibody ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Spike Protein ◽

Immunological Study ◽

Igg Antibody ◽

Vaccine Schedule

Abstract Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 in a cohort of patients who were previously infected with SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of SARS-CoV-2 infection were enrolled in our immunological study. The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5 – 327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time depends on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

Download Full-text

Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1800224115 ◽

2018 ◽

Vol 115 (24) ◽

pp. 6273-6278 ◽

Cited By ~ 53

Author(s):

Ilona Baraniak ◽

Barbara Kropff ◽

Lyn Ambrose ◽

Megan McIntosh ◽

Gary R. McLean ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

De Novo ◽

Natural Infection ◽

Neutralizing Antibody ◽

Glycoprotein B ◽

Solid Organ ◽

Viral Glycoprotein ◽

Viral Spread

Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro. Additionally, sera from seronegative vaccine recipients had minimal effect on the replication of a strain of HCMV engineered to be cell-associated in a viral spread assay. Furthermore, although natural infection can induce antibody-dependent cellular cytotoxicity (ADCC) responses, serological analysis of seronegative vaccinees again presented no evidence of a substantial ADCC-promoting antibody response being generated de novo. Finally, analyses for responses against major antigenic domains of gB following vaccination were variable, and their pattern was distinct compared with natural infection. Taken together, these data argue that the protective effect elicited by the gB vaccine is via a mechanism of action in seronegative vaccinees that cannot be explained by neutralization or the induction of ADCC. More generally, these data, which are derived from a human challenge model that demonstrated that the gB vaccine is protective, highlight the need for more sophisticated analyses of new HCMV vaccines over and above the quantification of an ability to induce potent neutralizing antibody responses in vitro.

Download Full-text

DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Elicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys

Journal of Virology ◽

10.1128/jvi.75.18.8469-8477.2001 ◽

2001 ◽

Vol 75 (18) ◽

pp. 8469-8477 ◽

Cited By ~ 84

Author(s):

J. W. Hooper ◽

D. M. Custer ◽

E. Thompson ◽

C. S. Schmaljohn

Keyword(s):

Antibody Response ◽

Rhesus Monkeys ◽

Neutralizing Antibodies ◽

Dna Vaccines ◽

Surrogate Marker ◽

Case Fatality ◽

Neutralizing Antibody ◽

Dna Vaccination ◽

Hantaan Virus ◽

M Gene

ABSTRACT Four hantaviruses—Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus—are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.

Download Full-text

Severe Acute Respiratory Syndrome-Associated Coronavirus Vaccines Formulated with Delta Inulin Adjuvants Provide Enhanced Protection while Ameliorating Lung Eosinophilic Immunopathology

Journal of Virology ◽

10.1128/jvi.02980-14 ◽

2014 ◽

Vol 89 (6) ◽

pp. 2995-3007 ◽

Cited By ~ 79

Author(s):

Yoshikazu Honda-Okubo ◽

Dale Barnard ◽

Chun Hao Ong ◽

Bi-Hung Peng ◽

Chien-Te Kent Tseng ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Case Fatality ◽

Neutralizing Antibody ◽

The Elderly ◽

Spike Protein ◽

Interleukin 4 ◽

Unique Problem ◽

Antibody Titers ◽

Ifn Γ

ABSTRACTAlthough the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses.IMPORTANCECoronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.

Download Full-text

Comparative Immunogenicity of Subtype A Human Immunodeficiency Virus Type 1 Envelope Exhibiting Differential Exposure of Conserved Neutralization Epitopes

Journal of Virology ◽

10.1128/jvi.01687-09 ◽

2009 ◽

Vol 84 (5) ◽

pp. 2573-2584 ◽

Cited By ~ 18

Author(s):

Catherine A. Blish ◽

D. Noah Sather ◽

George Sellhorn ◽

Leonidas Stamatatos ◽

Yide Sun ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Neutralizing Antibody ◽

Immunodeficiency Virus ◽

Cd4 Binding Site ◽

Variable Loops ◽

Linear Epitopes ◽

Subtype A ◽

Hiv 1

ABSTRACT Development of broadly cross-reactive neutralizing antibodies (NAbs) remains a major goal of HIV-1 vaccine development, but most candidate envelope immunogens have had limited ability to cross-neutralize heterologous strains. To evaluate the immunogenicity of subtype A variants of HIV-1, rabbits were immunized with pairs of closely related subtype A envelopes from the same individual. In each immunogen pair, one variant was readily neutralized by a variety of monoclonal antibodies and plasma antibodies, while the other was neutralization resistant, suggesting differences in the exposures of key epitopes. The breadth of the antibody response was evaluated against subtype A, B, C, and D variants of HIV-1. The specificity of the immunogen-derived neutralizing antibody response was also compared to that of the infected individuals from whom these variants were cloned. None of the immunogens produced broad neutralizing antibodies in immunized animals, and most of the neutralizing antibodies were directed to the variable loops, particularly the V3 loop. No detectable antibodies to either of the potentially exposed conserved epitopes, the membrane proximal external region, or the CD4 binding site were found with immunized rabbits. In contrast, relatively little of the neutralizing activity within the plasma samples of the infected individuals was directed to linear epitopes within the variable loops. These data indicate that immunogens designed to expose conserved regions did not enhance generation of broadly neutralizing antibodies in comparison with the immunogens that failed to expose those regions using this immunization approach.

Download Full-text