Special Issue "HIV and SARS-CoV-2 Pathogenesis and Vaccine Development"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: 30 June 2021.

Special Issue Editor

Dr. Herve J A Fleury
E-Mail
Guest Editor
CNRS MFP-UMR 5234, University Hospital of Bordeaux, University of Bordeaux, Bordeaux, France

Special Issue Information

Dear Colleagues,

The discovery of efficient antiretroviral drugs has been crucial in the struggle against HIV (particularly HIV-1), leading to the management of chronic infection with a long-term life expectancy. However, there is one major field of research where progress is not at the expected level—namely HIV vaccine, whether preventive or therapeutic. Preventive vaccines have been largely investigated but have been hampered by the high variability of the virus with a lack of cross neutralization. Therapeutic vaccines were launched by Jonas Salk very early in the history of HIV/AIDS and represent an interesting option for viral cure possibly in association with purging agents (“shock and kill”). Most aim to stimulate CD8+ T-cell reactivity against conserved epitopes of the archived virus; it is now clear that it is necessary to take into account the genetic background of patients and the role of immune checkpoints like PD-1. It is also important to consider a new therapeutic option based on silencing of the virus (“block and lock”).

SARS-CoV-2 virus has emerged from the animal reservoir at the end of 2019 and is now associated with the worst pandemic in humans since “Spanish flu” in 1918. There is a growing understanding of the virus in virology, and numerous potential vaccines based on neutralization of the spike using different techniques (mRNA, recombinant adenovirus, inactivated virus, etc.) are being investigated; however, no efficient anti-SARS-CoV-2 drug has been identified so far, and there is a race to develop an antiviral treatment for this viral infection.

This Special Issue is open to all researchers involved in the struggle against HIV and SARS-CoV-2; original articles and reviews are welcome mainly in the field of vaccine development but also in pathogenesis and antiviral drugs.

Dr. Herve J A Fleury
Guest Editor

Manuscript Submission Information

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Keywords

  • HIV
  • SARS-CoV-2
  • vaccine
  • antiviral drugs
  • pathophysiology
  • animal models

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Published Papers (9 papers)

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Research

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Communication
Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design
Viruses 2021, 13(5), 884; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050884 - 11 May 2021
Viewed by 357
Abstract
The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no licensed vaccine for the human [...] Read more.
The year 2021 marks the 40th anniversary since physicians recognized symptoms of the acquired immunodeficiency syndrome (AIDS), a disease that has since caused more than 30 million deaths worldwide. Despite the passing of four decades, there remains no licensed vaccine for the human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS. Despite the development of outstanding anti-retroviral drugs, there are currently more than one-half million deaths each year due to AIDS. Here, we revisit a conventional vaccine strategy used for protection against variable pathogens like HIV-1, which combines an array of diverse surface antigens. The strategy uses antibody recognition patterns to categorize viruses and their surface antigens into groups. Then a leader is assigned for each group and group leaders are formulated into vaccine cocktails. The group leaders are ‘natural mosaics’, because they share one or more epitope(s) with each of the other group members. We encourage the application of this conventional approach to HIV-1 vaccine design. We suggest that the partnering of an antibody-instructed envelope cocktail with new vaccine vectors will yield a successful vaccine in the HIV-1 field. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
Article
In Silico, In Vitro and In Cellulo Models for Monitoring SARS-CoV-2 Spike/Human ACE2 Complex, Viral Entry and Cell Fusion
Viruses 2021, 13(3), 365; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030365 - 25 Feb 2021
Viewed by 1273
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Productive SARS-CoV-2 infection relies on viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). Indeed, viral entry into cells is mostly mediated by [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Productive SARS-CoV-2 infection relies on viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). Indeed, viral entry into cells is mostly mediated by the early interaction between the viral spike protein S and its ACE2 receptor. The S/ACE2 complex is, thus, the first contact point between the incoming virus and its cellular target; consequently, it has been considered an attractive therapeutic target. To further characterize this interaction and the cellular processes engaged in the entry step of the virus, we set up various in silico, in vitro and in cellulo approaches that allowed us to specifically monitor the S/ACE2 association. We report here a computational model of the SARS-CoV-2 S/ACE2 complex, as well as its biochemical and biophysical monitoring using pulldown, AlphaLISA and biolayer interferometry (BLI) binding assays. This led us to determine the kinetic parameters of the S/ACE2 association and dissociation steps. In parallel to these in vitro approaches, we developed in cellulo transduction assays using SARS-CoV-2 pseudotyped lentiviral vectors and HEK293T-ACE2 cell lines generated in-house. This allowed us to recapitulate the early replication stage of the infection mediated by the S/ACE2 interaction and to detect cell fusion induced by the interaction. Finally, a cell imaging system was set up to directly monitor the S/ACE2 interaction in a cellular context and a flow cytometry assay was developed to quantify this association at the cell surface. Together, these different approaches are available for both basic and clinical research, aiming to characterize the entry step of the original SARS-CoV-2 strain and its variants as well as to investigate the possible chemical modulation of this interaction. All these models will help in identifying new antiviral agents and new chemical tools for dissecting the virus entry step. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Article
Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen
Viruses 2021, 13(2), 263; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020263 - 09 Feb 2021
Viewed by 611
Abstract
B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent [...] Read more.
B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent development of potent HIV immunogens, numerous questions are still open regarding GC reaction during early HIV/SIV infection. Here, we dissect the dynamics of B- and T-cells in GCs of macaques acutely infected by SIV (Group SIV+) or vaccinated with Tetanus Toxoid (Group TT), a T-dependent model antigen. Systemic inflammation and mobilization of antigen-presenting cells in inguinal lymph nodes and spleen are lower in Group TT than in Group SIV+. Despite spleen GC reaction of higher magnitude in Group SIV+, the development of protective immunity could be limited by abnormal helper functions of TFH massively polarized into TFH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of TFR limiting TFH/TFR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21lo memory B-cells, unable to further participate to GC reaction, likely contribute to eliminate SIV-specific B-cells and decrease antibody affinity maturation. Surprisingly, functional GCs and potent TT-specific antibodies develop despite low levels of CXCL13. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Article
Obstetric Outcomes of SARS-CoV-2 Infection in Asymptomatic Pregnant Women
Viruses 2021, 13(1), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010112 - 15 Jan 2021
Cited by 2 | Viewed by 2291
Abstract
Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared [...] Read more.
Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13–3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Review

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Review
A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis
Viruses 2021, 13(5), 931; https://0-doi-org.brum.beds.ac.uk/10.3390/v13050931 - 17 May 2021
Viewed by 495
Abstract
By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections [...] Read more.
By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
Review
In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?
Viruses 2021, 13(3), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/v13030501 - 18 Mar 2021
Viewed by 700
Abstract
Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for [...] Read more.
Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Review
HIV Vaccine Development: 35 Years of Experimenting in the Funding of Biomedical Research
Viruses 2020, 12(12), 1469; https://0-doi-org.brum.beds.ac.uk/10.3390/v12121469 - 19 Dec 2020
Viewed by 842
Abstract
Funding vaccine development research is more complicated than simply putting out an announcement of funds available. The funders must decide whether product development can be accomplished by purely applied research, or whether more fundamental knowledge is needed before product development can be started. [...] Read more.
Funding vaccine development research is more complicated than simply putting out an announcement of funds available. The funders must decide whether product development can be accomplished by purely applied research, or whether more fundamental knowledge is needed before product development can be started. If additional basic knowledge is needed, identifying the specific area of the knowledge gap can be a challenge. Additionally, when there appears to be a clear path of applied research sometimes obstacles are encountered that require a return to more basic work. After deciding on the work to be done, funders must attract the scientists with the broad range of needed skills to cover all the stages of development. Collaborations must be promoted and alliances with other funders and industry must be developed. Funders use multiple tools and strategies to accomplish these tasks with varying success. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Other

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Opinion
Virus Eradication and Synthetic Biology: Changes with SARS-CoV-2?
Viruses 2021, 13(4), 569; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040569 - 28 Mar 2021
Viewed by 739
Abstract
The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, [...] Read more.
The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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Brief Report
ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
Viruses 2020, 12(11), 1256; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111256 - 05 Nov 2020
Viewed by 684
Abstract
We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of [...] Read more.
We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker. Full article
(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)
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