Long-term Persistence of Neutralizing Antibodies to SARS-CoV-2 Following Infection

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

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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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Vectored Immunotherapeutics for Infectious Diseases: Can rAAVs Be The Game Changers for Fighting Transmissible Pathogens?

Frontiers in Immunology ◽

10.3389/fimmu.2021.673699 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wei Zhan ◽

Manish Muhuri ◽

Phillip W. L. Tai ◽

Guangping Gao

Keyword(s):

Infectious Diseases ◽

Neutralizing Antibodies ◽

Viral Vectors ◽

De Novo ◽

Genomic Variation ◽

Transduction Efficiency ◽

Foreign Proteins ◽

Repeated Dosing

Conventional vaccinations and immunotherapies have encountered major roadblocks in preventing infectious diseases like HIV, influenza, and malaria. These challenges are due to the high genomic variation and immunomodulatory mechanisms inherent to these diseases. Passive transfer of broadly neutralizing antibodies may offer partial protection, but these treatments require repeated dosing. Some recombinant viral vectors, such as those based on lentiviruses and adeno-associated viruses (AAVs), can confer long-term transgene expression in the host after a single dose. Particularly, recombinant (r)AAVs have emerged as favorable vectors, given their high in vivo transduction efficiency, proven clinical efficacy, and low immunogenicity profiles. Hence, rAAVs are being explored to deliver recombinant antibodies to confer immunity against infections or to diminish the severity of disease. When used as a vaccination vector for the delivery of antigens, rAAVs enable de novo synthesis of foreign proteins with the conformation and topology that resemble those of natural pathogens. However, technical hurdles like pre-existing immunity to the rAAV capsid and production of anti-drug antibodies can reduce the efficacy of rAAV-vectored immunotherapies. This review summarizes rAAV-based prophylactic and therapeutic strategies developed against infectious diseases that are currently being tested in pre-clinical and clinical studies. Technical challenges and potential solutions will also be discussed.

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Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers

Journal of Virology ◽

10.1128/jvi.01328-08 ◽

2008 ◽

Vol 83 (2) ◽

pp. 662-672 ◽

Cited By ~ 79

Author(s):

Madhumita Mahalanabis ◽

Pushpa Jayaraman ◽

Toshiyuki Miura ◽

Florencia Pereyra ◽

E. Michael Chester ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Neutralizing Antibodies ◽

Time Frame ◽

Continuous Selection ◽

Viral Escape ◽

Elite Controllers ◽

Hiv Replication ◽

Immunodeficiency Virus ◽

Short Time

ABSTRACT We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naïve subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous env evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive variants dominated in subjects with intermittent viral blips, while neutralization-resistant variants predominated in elite controllers. By sequence analysis of this panel of autologous variants with various sensitivities to neutralization, we identified more than 30 residues in envelope proteins (Env) associated with resistance or sensitivity to ANAbs. The appearance of new sensitive variants is consistent with a model of continuous selection and turnover. Strong ANAb responses directed against autologous Env variants are present in long-term chronically infected individuals, suggesting a role for these responses in contributing to the durable control of HIV replication.

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Chapter 14: Prevention: vaccines and immunoglobulins

Tick-borne encephalitis - The Book ◽

10.33442/26613980_14-4 ◽

2021 ◽

Author(s):

Eva-Maria Pöllabauer ◽

Herwig Kollaritsch

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Western Europe ◽

Surrogate Marker ◽

Booster Vaccination ◽

Post Exposure Prophylaxis ◽

Pediatric Formulation ◽

The One ◽

Exposure Prophylaxis

Worldwide there are 6 different TBE vaccines – two from Western Europe, three from Russia and one from China. The two western European vaccines and one of the Russian vaccines have an adult and a pediatric formulation. The products names are FSME IMMUN and FSME-IMMUN Junior; Encepur adults and Encepur children, Klesch-E-Vac, EnceVir and EnceVir Neo, Dry lyophilized TBE Moscow and Sen Tai Bao. All TBE vaccines except the one from China have similar but not identical immunization schedules with primary immunization (>3 doses) and regular booster vaccinations. For FSME-IMMUN, Encepur and EnceVir rapid immunization schedules are also licensed. The Chinese vaccine is given with 2 primary doses 2 weeks apart followed by annual boosters. All vaccines induce significant immune responses. In the absence of a formal correlate of protection, the presence of neutralizing antibodies is used as a surrogate marker for protection. Recent clinical studies show long-term seropersistence of TBE antibodies after the first booster vaccination (dose 4) with the two European vaccines. An effectiveness of approximately 99% (years 2000–2006) and 98.7% (years 2000-2011) was calculated for regularly vaccinated persons in Austria, a country with established high vaccination uptake. Whereas in Western Europe post-exposure prophylaxis with immunoglobulins was discontinued in the late 1990s, in the highly endemic regions of Russia it continues to be common practice. Both – FSME-IMMUN and Encepur are well tolerated with a well-established safety profile. TBE-Moscow and EnceVir appear to be somewhat more reactogenic.

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Longitudinal prospective evaluation of treatment effects, MRI and neutralizing antibodies in multiple sclerosis patients treated long-term with interferon-β-1b (Betaseron)

MULTIPLE SCLEROSIS ◽

10.4324/9780203212974_chapter_33 ◽

2010 ◽

pp. 317-322

Author(s):

Raymond M Hupperts ◽

Donald Paty ◽

David Li ◽

Joël Oger

Keyword(s):

Multiple Sclerosis ◽

Neutralizing Antibodies ◽

Treatment Effects ◽

Prospective Evaluation ◽

Interferon Β ◽

Multiple Sclerosis Patients

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Longitudinal prospective evaluation of treatment effects, MRI and neutralizing antibodies in multiple sclerosis patients treated long-term with interferon-β-1b (Betaseron®)

Multiple Sclerosis ◽

10.3109/9780203212974-47 ◽

2001 ◽

pp. 403-408

Keyword(s):

Multiple Sclerosis ◽

Neutralizing Antibodies ◽

Treatment Effects ◽

Prospective Evaluation ◽

Interferon Β ◽

Multiple Sclerosis Patients

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A Replicating Single-Cycle Adenovirus Vaccine Effective against Clostridium difficile

Vaccines ◽

10.3390/vaccines8030470 ◽

2020 ◽

Vol 8 (3) ◽

pp. 470

Author(s):

William E. Matchett ◽

Stephanie Anguiano-Zarate ◽

Goda Baddage Rakitha Malewana ◽

Haley Mudrick ◽

Melissa Weldy ◽

...

Keyword(s):

Clostridium Difficile ◽

Neutralizing Antibodies ◽

Antibody Responses ◽

Complete Protection ◽

Single Cycle ◽

Toxin B ◽

Toxin Binding ◽

Binding Domains ◽

Binding Antibody

Clostridium difficile causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. C. difficile infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against C. difficile’s toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against C. difficile expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans.

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Erratum to: ‘Cross-genotype AR3-specific neutralizing antibodies confer long-term protection in injecting drug users after HCV clearance’ (J Hepatol 2019; 71(1): 14-24)

Journal of Hepatology ◽

10.1016/j.jhep.2020.07.004 ◽

2020 ◽

Vol 73 (4) ◽

pp. 999-1000

Author(s):

Sabrina J. Merat ◽

Camille Bru ◽

Dorien van de Berg ◽

Richard Molenkamp ◽

Alexander W. Tarr ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Drug Users ◽

Injecting Drug Users

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MCP-1, not MIP-1α, Is the Endogenous Chemokine That Cooperates With TGF-β to Inhibit the Cycling of Primitive Normal but not Leukemic (CML) Progenitors in Long-Term Human Marrow Cultures

Blood ◽

10.1182/blood.v92.7.2338 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2338-2344 ◽

Cited By ~ 53

Author(s):

J.D. Cashman ◽

C.J. Eaves ◽

A.H. Sarris ◽

A.C. Eaves

Keyword(s):

Inhibitory Activity ◽

Neutralizing Antibodies ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Monocyte Chemoattractant Protein 1 ◽

Inflammatory Protein ◽

Progenitor Cell Proliferation ◽

Normal Human ◽

Macrophage Inflammatory Protein

Abstract The long-term culture (LTC) system has been useful for analyzing mechanisms by which stromal cells regulate the proliferative activity of primitive normal, but not chronic myeloid leukemia (CML), hematopoietic progenitor cells. In previous studies, we identified two endogenous inhibitors in this system. One is transforming growth factor-β (TGF-β), which is equally active on primitive normal and CML progenitors. The other we now show to be monocyte chemoattractant protein-1 (MCP-1). Thus, MCP-1, when added to LTC, blocked the activation of primitive normal progenitors but did not arrest the cycling of primitive CML progenitors. Moreover, the endogenous inhibitory activity of LTC stromal layers could be overcome by the addition of neutralizing antibodies to MCP-1, but not to macrophage inflammatory protein-1α (MIP-1α). However, neither of these antibodies antagonized the inhibitory activity of NAc-Ser-Asp-Lys-Pro (AcSDKP) on primitive normal but not CML progenitor cycling in this system. Moreover, none of six other -C-C- or -C-X-C- chemokines, previously shown to inhibit primitive normal human CFC proliferation in semisolid assays, were found to act as negative regulators when added to normal LTC. These results provide further support for the concept that primitive CML progenitor cell proliferation is deregulated when these cells are exposed to limiting concentrations of multiple inhibitors, only some of which have differential actions on normal and Ph+/BCR-ABL+ cells.

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