Correction for Nébié et al., Assessment of Chimpanzee Adenovirus Serotype 63 Neutralizing Antibodies Prior to Evaluation of a Candidate Malaria Vaccine Regimen Based on Viral Vectors

ABSTRACTPrior to a chimpanzee adenovirus-based (ChAd63) malarial vaccine trial, sera were collected to assess ChAd63-specific neutralizing antibody titers in Banfora (Burkina Faso). The low neutralizing antibody titers reported in both adults and children (median titers, 139.1 and 35.0, respectively) are encouraging for the potential use of ChAd63 as a malarial vaccine vector.

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Viral vectors in malaria vaccine development

Parasite Immunology ◽

10.1111/j.1365-3024.2009.01141.x ◽

2009 ◽

Vol 31 (9) ◽

pp. 501-519 ◽

Cited By ~ 38

Author(s):

K. J. LIMBACH ◽

T. L. RICHIE

Keyword(s):

Viral Vectors ◽

Malaria Vaccine ◽

Vaccine Development

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High Efficacy of a Low Dose Candidate Malaria Vaccine, R21 in 1 Adjuvant Matrix-M™, with Seasonal Administration to Children in Burkina Faso

SSRN Electronic Journal ◽

10.2139/ssrn.3830681 ◽

2021 ◽

Cited By ~ 1

Author(s):

Mehreen S. Datoo ◽

Hamtandi Magloire Natama ◽

Athanase Somé ◽

Ousmane Traoré ◽

Toussaint Rouamba ◽

...

Keyword(s):

Burkina Faso ◽

Malaria Vaccine ◽

Low Dose ◽

High Efficacy ◽

Candidate Malaria Vaccine

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Bacterially Expressed Full-Length Recombinant Plasmodium falciparum RH5 Protein Binds Erythrocytes and Elicits Potent Strain-Transcending Parasite-Neutralizing Antibodies

Infection and Immunity ◽

10.1128/iai.00970-13 ◽

2013 ◽

Vol 82 (1) ◽

pp. 152-164 ◽

Cited By ~ 54

Author(s):

K. Sony Reddy ◽

Alok K. Pandey ◽

Hina Singh ◽

Tajali Sahar ◽

Amlabu Emmanuel ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Neutralizing Antibodies ◽

Malaria Vaccine ◽

Expression System ◽

Full Length ◽

Blood Stage ◽

Parasite Protein ◽

Content Type ◽

Erythrocyte Binding ◽

Blood Stage Malaria

ABSTRACTPlasmodium falciparumreticulocyte binding-like homologous protein 5 (PfRH5) is an essential merozoite ligand that binds with its erythrocyte receptor, basigin. PfRH5 is an attractive malaria vaccine candidate, as it is expressed by a wide number ofP. falciparumstrains, cannot be genetically disrupted, and exhibits limited sequence polymorphisms. Viral vector-induced PfRH5 antibodies potently inhibited erythrocyte invasion. However, it has been a challenge to generate full-length recombinant PfRH5 in a bacterial-cell-based expression system. In this study, we have produced full-length recombinant PfRH5 inEscherichia colithat exhibits specific erythrocyte binding similar to that of the native PfRH5 parasite protein and also, importantly, elicits potent invasion-inhibitory antibodies against a number ofP. falciparumstrains. Antibasigin antibodies blocked the erythrocyte binding of both native and recombinant PfRH5, further confirming that they bind with basigin. We have thus successfully produced full-length PfRH5 as a functionally active erythrocyte binding recombinant protein with a conformational integrity that mimics that of the native parasite protein and elicits potent strain-transcending parasite-neutralizing antibodies.P. falciparumhas the capability to develop immune escape mechanisms, and thus, blood-stage malaria vaccines that target multiple antigens or pathways may prove to be highly efficacious. In this regard, antibody combinations targeting PfRH5 and other key merozoite antigens produced potent additive inhibition against multiple worldwideP. falciparumstrains. PfRH5 was immunogenic when immunized with other antigens, eliciting potent invasion-inhibitory antibody responses with no immune interference. Our results strongly support the development of PfRH5 as a component of a combination blood-stage malaria vaccine.

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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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Five year safety and immunogenicity of GlaxoSmithKline's candidate malaria vaccine RTS,S/AS02 following administration to semi-immune adult men living in a malaria-endemic region of The Gambia

Human Vaccines ◽

10.4161/hv.5.4.7050 ◽

2009 ◽

Vol 5 (4) ◽

pp. 242-247 ◽

Cited By ~ 25

Author(s):

Kalifa Bojang ◽

Paul Milligan ◽

Margaret Pinder ◽

Tom Doherty ◽

Amanda Leach ◽

...

Keyword(s):

Malaria Vaccine ◽

The Gambia ◽

Endemic Region ◽

Adult Men ◽

Malaria Endemic Region ◽

Candidate Malaria Vaccine

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Poly-Gamma-Glutamic Acid (γ-PGA)-Based Encapsulation of Adenovirus to Evade Neutralizing Antibodies

Molecules ◽

10.3390/molecules23102565 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2565 ◽

Cited By ~ 15

Author(s):

Ibrahim Khalil ◽

Martin Khechara ◽

Sathishkumar Kurusamy ◽

Angel Armesilla ◽

Abhishek Gupta ◽

...

Keyword(s):

Glutamic Acid ◽

Neutralizing Antibodies ◽

Viral Vectors ◽

Viral Vector ◽

Neutralizing Antibody ◽

Anticancer Therapy ◽

Significant Research ◽

Low Toxicity ◽

Cancerous Cells

In recent years, there has been an increasing interest in oncolytic adenoviral vectors as an alternative anticancer therapy. The induction of an immune response can be considered as a major limitation of this kind of application. Significant research efforts have been focused on the development of biodegradable polymer poly-gamma-glutamic acid (γ-PGA)-based nanoparticles used as a vector for effective and safe anticancer therapy, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. This study aimed to introduce a specific destructive and antibody blind polymer-coated viral vector into cancer cells using γ-PGA and chitosan (CH). Adenovirus was successfully encapsulated into the biopolymer particles with an encapsulation efficiency of 92% and particle size of 485 nm using the ionic gelation method. Therapeutic agents or nanoparticles (NPs) that carry therapeutics can be directed specifically to cancerous cells by decorating their surfaces using targeting ligands. Moreover, in vitro neutralizing antibody response against viral capsid proteins can be somewhat reduced by encapsulating adenovirus into γ-PGA-CH NPs, as only 3.1% of the encapsulated adenovirus was detected by anti-adenovirus antibodies in the presented work compared to naked adenoviruses. The results obtained and the unique characteristics of the polymer established in this research could provide a reference for the coating and controlled release of viral vectors used in anticancer therapy.

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Safety and Immunogenicity of Heterologous and Homologous 2-Dose Regimens of Adenovirus Serotype 26– and Modified Vaccinia Ankara–Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa586 ◽

2020 ◽

Cited By ~ 1

Author(s):

Neil Goldstein ◽

Viki Bockstal ◽

Stephan Bart ◽

Kerstin Luhn ◽

Cynthia Robinson ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Ebola Virus ◽

Phase 1 ◽

Booster Vaccination ◽

Controlled Study ◽

Adenovirus Serotype ◽

Cellular Immune Responses ◽

High Doses ◽

Cellular Immune

Abstract Background This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen.

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