The Effects of Checkpoint Blockade and a CD40 Agonist on Tindependent and T-dependent Antibody Responses in Mice: Implications for Optimization of Vaccination Strategies in Patients Receiving Immunotherapies

ABSTRACT Individuals living in regions of intense malaria transmission exhibit natural immunity that facilitates persistence of parasitemia at controlled densities for much of the time without symptoms. This aspect of immunity has been referred to as malarial “tolerance” and is thought to partly involve inhibition of the chain of events initiated by a parasite toxin(s) that may otherwise result in cytokine release and symptoms such as fever. Antibodies to the candidate Plasmodium falciparum glycosylphosphatidylinositol (GPI) toxin have been viewed as likely mediators of such tolerance. In this study, the relationship between antibodies to P. falciparum GPIs, age, and parasitemia was determined in asymptomatic children and adults living in Madang, Papua New Guinea. The prevalence and intensity of antibody responses increased with age and were lowest in children 1 to 4 years old with the highest-density parasitemias. In children of this age group who were tolerant of parasitemia during the study, only 8.3% had detectable immunoglobulin G (IgG) and none had IgM antibodies to GPI. This suggests that anti-GPI antibodies are unlikely to be the sole mediator of malarial tolerance, especially in children younger than 5 years. Following antimalarial treatment, clearance of parasitemia led to a fall in anti-GPI IgG response in children and adolescents within 6 weeks. As anti-GPI antibodies potentially play a role in protecting against disease progression, our results caution against the treatment of asymptomatic parasitemia and suggest that generation of a sustained antibody response in children poses a challenge to novel antitoxic vaccination strategies.

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Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice

Virology Journal ◽

10.1186/s12985-021-01737-3 ◽

2022 ◽

Vol 19 (1) ◽

Author(s):

Shuo Song ◽

Bing Zhou ◽

Lin Cheng ◽

Weilong Liu ◽

Qing Fan ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Booster Dose ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Inactivated Vaccine ◽

Wild Type ◽

Broadly Neutralizing Antibodies ◽

Vaccination Strategies ◽

Inactivated Vaccines

AbstractThe current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

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Antibody Responses to Natural SARS-CoV-2 Infection or after COVID-19 Vaccination

Vaccines ◽

10.3390/vaccines9080910 ◽

2021 ◽

Vol 9 (8) ◽

pp. 910

Author(s):

Haya Altawalah

Keyword(s):

Public Health ◽

Immune Response ◽

Antibody Responses ◽

Clinical Severity ◽

The Novel ◽

Protective Capacity ◽

Humoral Immune ◽

Vaccination Strategies ◽

First Case ◽

Novel Coronavirus

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19). The clinical severity of COVID-19 ranges from asymptomatic to critical disease and, eventually, death in smaller subsets of patients. The first case of COVID-19 was declared at the end of 2019 and it has since spread worldwide and remained a challenge in 2021, with the emergence of variants of concern. In fact, new concerns were the still unclear situation of SARS-CoV-2 immunity during the ongoing pandemic and progress with vaccination. If maintained at sufficiently high levels, the immune response could effectively block reinfection, which might confer long-lived protection. Understanding the protective capacity and the duration of humoral immunity during SARS-CoV-2 infection or after vaccination is critical for managing the pandemic and would also provide more evidence about the efficacy of SARS-CoV-2 vaccines. However, the exact features of antibody responses that govern SARS-CoV-2 infection or after vaccination remain unclear. This review summarizes the main knowledge that we have about the humoral immune response during COVID-19 disease or after vaccination. Such knowledge should help to optimize vaccination strategies and public health decisions.

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Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up

10.1101/2021.09.18.21263550 ◽

2021 ◽

Author(s):

Yang Yang ◽

Minghui Yang ◽

Yun Peng ◽

Yanhua Liang ◽

Jinli Wei ◽

...

Keyword(s):

Neutralizing Antibody ◽

Antibody Responses ◽

Clinical Spectrum ◽

Neutralizing Activity ◽

Vaccination Strategies ◽

Subsequent Decrease ◽

Asymptomatic Infections ◽

One Year ◽

Kinetics Of

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400~480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with ≥ 50% decrease in MN titers when comparing the available peak and current MN titers (≥ 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

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Differential Antibody Response to Inactivated COVID-19 Vaccines in Healthy Subjects

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.791660 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiaqi Zhang ◽

Shan Xing ◽

Dan Liang ◽

Wei Hu ◽

Changwen Ke ◽

...

Keyword(s):

Blood Parameters ◽

Antibody Responses ◽

Blood Parameter ◽

Dynamic Changes ◽

Related Factors ◽

Vaccination Strategies ◽

Elderly Recipients ◽

Inactivated Vaccines ◽

Insight Into ◽

Estradiol Levels

The appearance and magnitude of the immune response and the related factors correlated with SARS-CoV-2 vaccination need to be defined. Here, we enrolled a prospective cohort of 52 participants who received two doses of inactivated vaccines (BBIBP-CorV). Their serial plasma samples (n = 260) over 2 months were collected at five timepoints. We measured antibody responses (NAb, S-IgG and S-IgM) and routine blood parameter. NAb seroconversion occurred in 90.7% of vaccinated individuals and four typical NAb kinetic curves were observed. All of the participants who seroconverted after the first dose were females and had relatively high prevaccine estradiol levels. Moreover, those without seroconversion tended to have lower lymphocyte counts and higher serum SAA levels than those who experienced seroconversion. The NAb titers in young vaccine recipients had a significantly higher peak than those in elderly recipients. S-IgG and S-IgM dynamics were accompanied by similar trends in NAb. Here, we gained insight into the dynamic changes in NAbs and preliminarily explored the prevaccine blood parameters related to the kinetic subclasses, providing a reference for vaccination strategies.

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Exposures to different SARS-CoV-2 spike variants elicit neutralizing antibody responses with differential specificity towards established and emerging strains

10.1101/2021.09.08.21263095 ◽

2021 ◽

Author(s):

Matthew T Laurie ◽

Jamin Liu ◽

Sara Sunshine ◽

James Peng ◽

Douglas Black ◽

...

Keyword(s):

Immune Response ◽

Wide Spectrum ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Spike Protein ◽

Vaccination Strategies ◽

Cross Neutralization ◽

The Relationship

The wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing one or more spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding the relationship between exposures and antibody responses and may inform booster vaccination strategies.

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SARS-CoV-2 antibody responses determine disease severity in COVID-19 infected individuals

10.1101/2020.07.27.20162321 ◽

2020 ◽

Cited By ~ 2

Author(s):

Cecilie Bo Hansen ◽

Ida Jarlhelt ◽

Laura Pérez-Alós ◽

Lone Hummelshøj Landsy ◽

Mette Loftager ◽

...

Keyword(s):

Disease Severity ◽

Receptor Binding ◽

Large Population ◽

Sandwich Elisa ◽

Antibody Responses ◽

Diagnostic Tools ◽

Receptor Binding Domain ◽

Specific Detection ◽

Vaccination Strategies

Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and calls for diagnostic tools to monitor and understand the transmission, pathogenesis and epidemiology, as well as to evaluate future vaccination strategies. Here we have developed novel flexible ELISA-based assays for specific detection of SARS-CoV-2 antibodies against the receptor-binding domain (RBD): An antigen sandwich-ELISA relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection, ranging from asymptomatic to critical cases. We mapped the antibody responses to different areas on protein N and S and showed that the IgM, A and G antibody responses against RBD are significantly correlated to the disease severity. These assays-and the data generated from them-are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.

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Virus-like particles (VLPs) are efficient tools for boosting mRNA-induced antibodies

10.1101/2021.12.20.473421 ◽

2021 ◽

Author(s):

Anne-Cathrine Sarah Vogt ◽

Lukas Jörg ◽

Byron Martina ◽

Pascal S. Krenger ◽

Xinyue Chang ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Vaccine Candidate ◽

Antibody Responses ◽

High Avidity ◽

Virus Like Particles ◽

Safety Issues ◽

Vaccination Strategies ◽

Boost Vaccination ◽

Shortage Costs

mRNA based vaccines against COVID-19 have proven most successful at keeping the SARS-CoV-2 pandemic at bay in many countries. Recently, there is an increased interest in heterologous prime-boost vaccination strategies for COVID-19 to maintain antibody response for the control of continuously emerging SARS-CoV-2 variants of concern (VoCs) and to overcome other obstacles such as supply shortage, costs and reduced safety issues or inadequate induced immune-response. In this study, we investigate the antibody responses induced by heterologous prime-boost with vaccines based on mRNA and virus-like particles (VLPs). The VLP-based CuMV TT -RBM vaccine candidate and the approved mRNA-1273 vaccine were used for this purpose. We find that homologous prime boost regimens with either mRNA or VLP induced high levels of high avidity antibodies. Optimal antibody responses were, however, induced by heterologous regimens both for priming with mRNA and boosting with VLP and vice versa, priming with VLP and boosting with mRNA. Thus, heterologous prime boost strategies may be able to optimize efficacy and economics of novel vaccine strategies.

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