Editorial

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2 pages, 172 KiB

Open AccessEditorial

HIV and SARS-CoV-2 Pathogenesis and Vaccine Development

by Herve Fleury

Viruses 2022, 14(12), 2598; https://doi.org/10.3390/v14122598 - 22 Nov 2022

Cited by 1 | Viewed by 814

Abstract

Although both HIV and SARS-CoV-2 are associated with pandemics, they are transmitted differently [...] Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

Research

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32 pages, 14771 KiB

Open AccessArticle

Fatal Neurodissemination and SARS-CoV-2 Tropism in K18-hACE2 Mice Is Only Partially Dependent on hACE2 Expression

by Mariano Carossino, Devin Kenney, Aoife K. O’Connell, Paige Montanaro, Anna E. Tseng, Hans P. Gertje, Kyle A. Grosz, Maria Ericsson, Bertrand R. Huber, Susanna A. Kurnick, Saravanan Subramaniam, Thomas A. Kirkland, Joel R. Walker, Kevin P. Francis, Alexander D. Klose, Neal Paragas, Markus Bosmann, Mohsan Saeed, Udeni B. R. Balasuriya, Florian Douam and Nicholas A. Crossland Show full author list Hide full author list

Viruses 2022, 14(3), 535; https://doi.org/10.3390/v14030535 - 05 Mar 2022

Cited by 42 | Viewed by 4644

Abstract

Animal models recapitulating COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Intranasally inoculated transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. We evaluated the clinical and virological dynamics of [...] Read more.

Animal models recapitulating COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Intranasally inoculated transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. We evaluated the clinical and virological dynamics of SARS-CoV-2 using two intranasal doses (10⁴ and 10⁶ PFUs), with a detailed spatiotemporal pathologic analysis of the 10⁶ dose cohort. Despite generally mild-to-moderate pneumonia, clinical decline resulting in euthanasia or death was commonly associated with hypothermia and viral neurodissemination independent of inoculation dose. Neuroinvasion was first observed at 4 days post-infection, initially restricted to the olfactory bulb suggesting axonal transport via the olfactory neuroepithelium as the earliest portal of entry. Absence of viremia suggests neuroinvasion occurs independently of transport across the blood-brain barrier. SARS-CoV-2 tropism was neither restricted to ACE2-expressing cells (e.g., AT1 pneumocytes), nor inclusive of some ACE2-positive cell lineages (e.g., bronchiolar epithelium and brain vasculature). Absence of detectable ACE2 protein expression in neurons but overexpression in neuroepithelium suggest this as the most likely portal of neuroinvasion, with subsequent ACE2 independent lethal neurodissemination. A paucity of epidemiological data and contradicting evidence for neuroinvasion and neurodissemination in humans call into question the translational relevance of this model. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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11 pages, 265 KiB

Open AccessArticle

Factors Associated with Severe COVID-19 and Post-Acute COVID-19 Syndrome in a Cohort of People Living with HIV on Antiretroviral Treatment and with Undetectable HIV RNA

by Maria Mazzitelli, Mattia Trunfio, Lolita Sasset, Davide Leoni, Eleonora Castelli, Sara Lo Menzo, Samuele Gardin, Cristina Putaggio, Monica Brundu, Pietro Garzotto and Anna Maria Cattelan

Viruses 2022, 14(3), 493; https://doi.org/10.3390/v14030493 - 28 Feb 2022

Cited by 15 | Viewed by 2701

Abstract

SARS-CoV-2 can produce both severe clinical conditions and long-term sequelae, but data describing post-acute COVID-19 syndrome (PACS) are lacking for people living with HIV (PLWH). We aimed at assessing the prevalence and factors associated with severe COVID-19 and PACS in our cohort. We [...] Read more.

SARS-CoV-2 can produce both severe clinical conditions and long-term sequelae, but data describing post-acute COVID-19 syndrome (PACS) are lacking for people living with HIV (PLWH). We aimed at assessing the prevalence and factors associated with severe COVID-19 and PACS in our cohort. We included all unvaccinated adult PLWH on antiretroviral treatment and plasma HIV-RNA < 40 cp/mL since at least six months before SARS-CoV-2 infection at the Infectious and Tropical Diseases Unit of Padua (Italy), from 20 February 2020 to 31 March 2021. COVID-19 severity was defined by WHO criteria; PACS was defined as the persistence of symptoms or development of sequelae beyond four weeks from SARS-CoV-2 infection. Demographic and clinical variables were collected, and data were analyzed by non-parametric tests. 123 subjects meeting the inclusion criteria among 1800 (6.8%) PLWH in care at the Infectious and Tropical diseases Unit in Padua were diagnosed with SARS-CoV-2 infection/COVID-19 during the study period. The median age was 51 years (40–58), 79.7% were males, and 77.2% of Caucasian ethnicity. The median CD4+ T-cell count and length of HIV infection were 560 cells/mmc (444–780) and 11 years, respectively. Of the patients, 35.0% had asymptomatic SARS-CoV-2 infection, 48% developed mild COVID-19, 17.1% presented moderate or severe COVID-19 requiring hospitalization and 4.1% died. Polypharmacy was the single independent factor associated with severe COVID-19. As for PACS, among 75 patients who survived SARS-CoV-2 symptomatic infection, 20 (26.7%) reported PACS at a median follow-up of six months: asthenia (80.0%), shortness of breath (50.0%) and recurrent headache (25.0%) were the three most common complaints. Only the severity of the COVID-19 episode predicted PACS after adjusting for relevant demographic and clinical variables. In our study, PLWH with sustained viral suppression and good immunological response showed that the risk of hospital admission for COVID-19 was low, even though the severity of the disease was associated with high mortality. In addition, the likelihood of developing severe COVID-19 and PACS was mainly driven by similar risk factors to those faced by the general population, such as polypharmacy and the severity of SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

17 pages, 2369 KiB

Open AccessArticle

Modulation of HIV Replication in Monocyte-Derived Macrophages (MDM) by Host Antiviral Factors Secretory Leukocyte Protease Inhibitor and Serpin Family C Member 1 Induced by Steroid Hormones

by Santanu Biswas, Emily Chen, Yamei Gao, Sherwin Lee, Indira Hewlett and Krishnakumar Devadas

Viruses 2022, 14(1), 95; https://doi.org/10.3390/v14010095 - 06 Jan 2022

Cited by 2 | Viewed by 2001

Abstract

The impact of steroid hormones estrogen and progesterone on human immunodeficiency virus type 1 (HIV-1) replication is well documented. However, the exact mechanism involved in the regulation of HIV-1 replication by estrogen and progesterone is still unclear. In the present study, we wanted [...] Read more.

The impact of steroid hormones estrogen and progesterone on human immunodeficiency virus type 1 (HIV-1) replication is well documented. However, the exact mechanism involved in the regulation of HIV-1 replication by estrogen and progesterone is still unclear. In the present study, we wanted to elucidate the molecular mechanisms underlying the modulation of HIV-1 replication by estrogen and progesterone. To achieve this goal, we used real-time quantitative PCR arrays (PCR arrays) to identify differentially expressed host genes in response to hormone treatments that are involved in antiviral responses. Our in vitro results suggest that treatment with high doses of estrogen and progesterone promotes the expression of host antiviral factors Secretory leukocyte protease inhibitor (SLPI) and Serpin family C member 1 (SERPIN C1) among others produced in response to HIV-1 infection. SLPI is an enzyme that inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. SERPIN C1 is a plasma protease inhibitor that regulates the blood coagulation cascade by the inhibition of thrombin and other activated serine proteases of the coagulation system. A dose dependent downmodulation of HIV-1 replication was observed in monocyte-derived macrophages (MDMs) pre-treated with the two proteins SLPI and SERPIN C1. Further investigations suggests that the host antiviral factors, SLPI and SERPIN C1 act at the pre-integration stage, inhibiting HIV-1 viral entry and leading to the observed downmodulation of HIV-1 replication. Our studies would help identify molecular mechanisms and pathways involved in HIV-1 pathogenesis. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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18 pages, 2588 KiB

Open AccessArticle

Peritoneal Administration of a Subunit Vaccine Encapsulated in a Nanodelivery System Not Only Augments Systemic Responses against SARS-CoV-2 but Also Stimulates Responses in the Respiratory Tract

by Tuksin Jearanaiwitayakul, Suttikarn Apichirapokey, Runglawan Chawengkirttikul, Jitra Limthongkul, Mathurin Seesen, Phissinee Jakaew, Sakalin Trisiriwanich, Sompong Sapsutthipas, Panya Sunintaboon and Sukathida Ubol

Viruses 2021, 13(11), 2202; https://doi.org/10.3390/v13112202 - 02 Nov 2021

Cited by 9 | Viewed by 2672

Abstract

The COVID-19 pandemic has currently created an unprecedented threat to human society and global health. A rapid mass vaccination to create herd immunity against SARS-CoV-2 is a crucial measure to ease the spread of this disease. Here, we investigated the immunogenicity of a [...] Read more.

The COVID-19 pandemic has currently created an unprecedented threat to human society and global health. A rapid mass vaccination to create herd immunity against SARS-CoV-2 is a crucial measure to ease the spread of this disease. Here, we investigated the immunogenicity of a SARS-CoV-2 subunit vaccine candidate, a SARS-CoV-2 spike glycoprotein encapsulated in N,N,N-trimethyl chitosan particles or S-TMC NPs. Upon intraperitoneal immunization, S-TMC NP-immunized mice elicited a stronger systemic antibody response, with neutralizing capacity against SARS-CoV-2, than mice receiving the soluble form of S-glycoprotein. S-TMC NPs were able to stimulate the circulating IgG and IgA as found in SARS-CoV-2-infected patients. In addition, spike-specific T cell responses were drastically activated in S-TMC NP-immunized mice. Surprisingly, administration of S-TMC NPs via the intraperitoneal route also stimulated SARS-CoV-2-specific immune responses in the respiratory tract, which were demonstrated by the presence of high levels of SARS-CoV-2-specific IgG and IgA in the lung homogenates and bronchoalveolar lavages of the immunized mice. We found that peritoneal immunization with spike nanospheres stimulates both systemic and respiratory mucosal immunity. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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19 pages, 2179 KiB

Open AccessArticle

Plant-Produced Glycosylated and In Vivo Deglycosylated Receptor Binding Domain Proteins of SARS-CoV-2 Induce Potent Neutralizing Responses in Mice

by Tarlan Mamedov, Damla Yuksel, Merve Ilgın, Irem Gurbuzaslan, Burcu Gulec, Hazel Yetiskin, Muhammet Ali Uygut, Shaikh Terkis Islam Pavel, Aykut Ozdarendeli, Gulshan Mammadova, Deniz Say and Gulnara Hasanova

Viruses 2021, 13(8), 1595; https://doi.org/10.3390/v13081595 - 12 Aug 2021

Cited by 22 | Viewed by 5048

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs cost-effective and safe SARS-CoV-2 vaccines, antiviral, and therapeutic drugs to control it. In this study, we [...] Read more.

The COVID-19 pandemic, caused by SARS-CoV-2, has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs cost-effective and safe SARS-CoV-2 vaccines, antiviral, and therapeutic drugs to control it. In this study, we engineered the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and produced it in the plant Nicotiana benthamiana in a glycosylated and deglycosylated form. Expression levels of both glycosylated (gRBD) and deglycosylated (dRBD) RBD were greater than 45 mg/kg fresh weight. The purification yields were 22 mg of pure protein/kg of plant biomass for gRBD and 20 mg for dRBD, which would be sufficient for commercialization of these vaccine candidates. The purified plant-produced RBD protein was recognized by an S protein-specific monoclonal antibody, demonstrating specific reactivity of the antibody to the plant-produced RBD proteins. The SARS-CoV-2 RBD showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. In mice, the plant-produced RBD antigens elicited high titers of antibodies with a potent virus-neutralizing activity. To our knowledge, this is the first report demonstrating that mice immunized with plant-produced deglycosylated RBD form elicited high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2 infection. Thus, obtained data support that plant-produced glycosylated and in vivo deglycosylated RBD antigens, developed in this study, are promising vaccine candidates for the prevention of COVID-19. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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12 pages, 240 KiB

Open AccessCommunication

Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design

by Robert E. Sealy, Barry Dayton, David Finkelstein and Julia L. Hurwitz

Viruses 2021, 13(5), 884; https://doi.org/10.3390/v13050884 - 11 May 2021

Cited by 1 | Viewed by 2354

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)

18 pages, 5307 KiB

Open AccessArticle

In Silico, In Vitro and In Cellulo Models for Monitoring SARS-CoV-2 Spike/Human ACE2 Complex, Viral Entry and Cell Fusion

by Delphine Lapaillerie, Cathy Charlier, Henrique S. Fernandes, Sergio F. Sousa, Paul Lesbats, Pierre Weigel, Alexandre Favereaux, Véronique Guyonnet-Duperat and Vincent Parissi

Viruses 2021, 13(3), 365; https://doi.org/10.3390/v13030365 - 25 Feb 2021

Cited by 12 | Viewed by 4464

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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20 pages, 2666 KiB

Open AccessArticle

Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen

by Maria Trovato, Hany M. Ibrahim, Stephane Isnard, Roger Le Grand, Nathalie Bosquet, Gwenoline Borhis and Yolande Richard

Viruses 2021, 13(2), 263; https://doi.org/10.3390/v13020263 - 09 Feb 2021

Cited by 3 | Viewed by 2406

Abstract

B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (T_FH) and regulatory (T_FR) 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 (T_FH) and regulatory (T_FR) 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 T_FH massively polarized into T_FH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of T_FR limiting T_FH/T_FR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21^lo 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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12 pages, 628 KiB

Open AccessArticle

Obstetric Outcomes of SARS-CoV-2 Infection in Asymptomatic Pregnant Women

by Monica Cruz-Lemini, Elena Ferriols Perez, Maria Luisa de la Cruz Conty, Africa Caño Aguilar, Maria Begoña Encinas Pardilla, Pilar Prats Rodríguez, Marta Muner Hernando, Laura Forcen Acebal, Pilar Pintado Recarte, Maria del Carmen Medina Mallen, Noelia Perez Perez, Judit Canet Rodriguez, Ana Villalba Yarza, Olga Nieto Velasco, Pablo Guillermo del Barrio Fernandez, Carmen Maria Orizales Lago, Beatriz Marcos Puig, Begoña Muñoz Abellana, Laura Fuentes Ricoy, Agueda Rodriguez Vicente, Maria Jesus Janeiro Freire, Macarena Alferez Alvarez-Mallo, Cristina Casanova Pedraz, Onofre Alomar Mateu, Cristina Lesmes Heredia, Juan Carlos Wizner de Alva, Alma Posadas San Juan, Montserrat Macia Badia, Cristina Alvarez Colomo, Antonio Sanchez Muñoz, Laia Pratcorona Alicart, Ruben Alonso Saiz, Monica Lopez Rodriguez, Maria Carmen Barbancho Lopez, Marta Ruth Meca Casbas, Oscar Vaquerizo Ruiz, Eva Moran Antolin, Maria Jose Nuñez Valera, Camino Fernandez Fernandez, Albert Tubau Navarra, Alejandra Maria Cano Garcia, Susana Soldevilla Perez, Irene Gattaca Abasolo, Jose Adanez Garcia, Alberto Puertas Prieto, Rosa Ostos Serna, Maria del Pilar Guadix Martin, Monica Catalina Coello, Silvia Espuelas Malon, Jose Antonio Sainz Bueno, Maria Reyes Granell Escobar, Sara Cruz Melguizo, Oscar Martinez Perez and on behalf of the Spanish Obstetric Emergency Group Show full author list Hide full author list

Viruses 2021, 13(1), 112; https://doi.org/10.3390/v13010112 - 15 Jan 2021

Cited by 34 | Viewed by 7445

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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19 pages, 505 KiB

Open AccessReview

mRNA- and Adenovirus-Based Vaccines against SARS-CoV-2 in HIV-Positive People

by Anna Rosa Garbuglia, Claudia Minosse and Paola Del Porto

Viruses 2022, 14(4), 748; https://doi.org/10.3390/v14040748 - 01 Apr 2022

Cited by 11 | Viewed by 3645

Abstract

About two years have passed since the identification of SARS-CoV-2 in China. The rapid spread of this virus all over the world and its high transmissibility and pathogenicity in humans have resulted in a global pandemic. The negative impact of COVID-19 on health, [...] Read more.

About two years have passed since the identification of SARS-CoV-2 in China. The rapid spread of this virus all over the world and its high transmissibility and pathogenicity in humans have resulted in a global pandemic. The negative impact of COVID-19 on health, society and the economy at the global level has pushed researchers and pharmaceutical companies to develop effective vaccines to fight SARS-CoV-2. Thanks to this collaborative effort, the first COVID-19 vaccine was developed in less than a year. Since then, several COVID-19 vaccines have been validated for use by the World Health Organization. Among these, mRNA- (BNT162b2 and mRNA1273) and adenovirus-based (ChAdOx1) vaccines were developed through the use of novel technologies. While all three of these vaccines have shown effectiveness against the COVID-19 disease and their immunogenicity was characterized in clinical trials in the general population, data on their efficacy and immunogenicity in people living with HIV (PLWH) are limited. In this review, we provide a description of the characteristics of mRNA- and adenovirus-based vaccines and of the immune response elicited in the general population by vaccination. Then we describe the use of these vaccines and their efficacy and immunogenicity in people living with HIV and we conclude with a discussion regarding some open questions concerning the use of mRNA- and adenovirus-based COVID-19 vaccines in PLWH. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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44 pages, 1567 KiB

Open AccessReview

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

by David A. Meekins, Natasha N. Gaudreault and Juergen A. Richt

Viruses 2021, 13(10), 1993; https://doi.org/10.3390/v13101993 - 04 Oct 2021

Cited by 57 | Viewed by 15192

Abstract

SARS-CoV-2 is the etiological agent responsible for the ongoing COVID-19 pandemic, which continues to spread with devastating effects on global health and socioeconomics. The susceptibility of domestic and wild animal species to infection is a critical facet of SARS-CoV-2 ecology, since reverse zoonotic [...] Read more.

SARS-CoV-2 is the etiological agent responsible for the ongoing COVID-19 pandemic, which continues to spread with devastating effects on global health and socioeconomics. The susceptibility of domestic and wild animal species to infection is a critical facet of SARS-CoV-2 ecology, since reverse zoonotic spillover events resulting in SARS-CoV-2 outbreaks in animal populations could result in the establishment of new virus reservoirs. Adaptive mutations in the virus to new animal species could also complicate ongoing mitigation strategies to combat SARS-CoV-2. In addition, animal species susceptible to SARS-CoV-2 infection are essential as standardized preclinical models for the development and efficacy testing of vaccines and therapeutics. In this review, we summarize the current findings regarding the susceptibility of different domestic and wild animal species to experimental SARS-CoV-2 infection and provide detailed descriptions of the clinical disease and transmissibility in these animals. In addition, we outline the documented natural infections in animals that have occurred at the human–animal interface. A comprehensive understanding of animal susceptibility to SARS-CoV-2 is crucial to inform public health, veterinary, and agricultural systems, and to guide environmental policies. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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16 pages, 451 KiB

Open AccessReview

COVID-19 Vaccines for HIV-Infected Patients

by Maria M. Plummer and Charles S. Pavia

Viruses 2021, 13(10), 1890; https://doi.org/10.3390/v13101890 - 22 Sep 2021

Cited by 10 | Viewed by 4265

Abstract

Nearly 40 years have passed since the initial cases of infection with the human mmunodeficiency virus (HIV) were identified as a new disease entity and the cause of acquired immunodeficiency disease (AIDS). This virus, unlike any other, is capable of causing severe suppression [...] Read more.

Nearly 40 years have passed since the initial cases of infection with the human mmunodeficiency virus (HIV) were identified as a new disease entity and the cause of acquired immunodeficiency disease (AIDS). This virus, unlike any other, is capable of causing severe suppression of our adaptive immune defense mechanisms by directly infecting and destroying helper T cells leading to increased susceptibility to a wide variety of microbial pathogens, especially those considered to be intracellular or opportunistic. After T cells are infected, HIV reproduces itself via a somewhat unique mechanism involving various metabolic steps, which includes the use of a reverse transcriptase enzyme that enables the viral RNA to produce copies of its complementary DNA. Subsequent physiologic steps lead to the production of new virus progeny and the eventual death of the invaded T cell. Fortunately, both serologic and molecular tests (such as PCR) can be used to confirm the diagnosis of an HIV infection. In the wake of the current COVID-19 pandemic, it appears that people living with HIV/AIDS are equally or slightly more susceptible to the etiologic agent, SARS-CoV-2, than the general population having intact immune systems, but they may have more serious outcomes. Limited clinical trials have also shown that the currently available COVID-19 vaccines are both safe and effective in affording protection to HIV/AIDS patients. In this review, we further explore the unique dynamic of HIV/AIDS in the context of the worldwide COVID-19 pandemic and the implementation of vaccines as a protective measure against COVID-19, as well as what immune parameters and safeguards should be monitored in this immunocompromised group following vaccination. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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31 pages, 3785 KiB

Open AccessReview

SARS-CoV-2 Infection: New Molecular, Phylogenetic, and Pathogenetic Insights. Efficacy of Current Vaccines and the Potential Risk of Variants

by John Charles Rotondo, Fernanda Martini, Martina Maritati, Chiara Mazziotta, Giulia Di Mauro, Carmen Lanzillotti, Nicole Barp, Altea Gallerani, Mauro Tognon and Carlo Contini

Viruses 2021, 13(9), 1687; https://doi.org/10.3390/v13091687 - 25 Aug 2021

Cited by 55 | Viewed by 6554

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 has rapidly become a public health emergency of international concern. Although remarkable scientific achievements have been reached since the beginning of the [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 has rapidly become a public health emergency of international concern. Although remarkable scientific achievements have been reached since the beginning of the pandemic, the knowledge behind this novel coronavirus, in terms of molecular and pathogenic characteristics and zoonotic potential, is still relatively limited. Today, there is a vaccine, or rather several vaccines, which, for the first time in the history of highly contagious infectious diseases that have plagued mankind, has been manufactured in just one year. Currently, four vaccines are licensed by regulatory agencies, and they use RNA or viral vector technologies. The positive effects of the vaccination campaign are being felt in many parts of the world, but the disappearance of this new infection is still far from being a reality, as it is also threatened by the presence of novel SARS-CoV-2 variants that could undermine the effectiveness of the vaccine, hampering the immunization control efforts. Indeed, the current findings indicate that SARS-CoV-2 is adapting to transmission in humans more efficiently, while further divergence from the initial archetype should be considered. In this review, we aimed to provide a collection of the current knowledge regarding the molecular, phylogenetic, and pathogenetic insights into SARS-CoV-2. The most recent findings obtained with respect to the impact of novel emerging SARS-CoV-2 variants as well as the development and implementation of vaccines are highlighted. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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12 pages, 741 KiB

Open AccessReview

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

by Léna Royston, Stéphane Isnard, John Lin and Jean-Pierre Routy

Viruses 2021, 13(7), 1266; https://doi.org/10.3390/v13071266 - 29 Jun 2021

Cited by 13 | Viewed by 3413

Abstract

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with [...] Read more.

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH. Full article

(This article belongs to the Special Issue HIV and SARS-CoV-2 Pathogenesis and Vaccine Development)

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13 pages, 282 KiB

Open AccessReview

A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis

by Carmen María González-Domenech, Isabel Pérez-Hernández, Cristina Gómez-Ayerbe, Isabel Viciana Ramos, Rosario Palacios-Muñoz and Jesús Santos

Viruses 2021, 13(5), 931; https://doi.org/10.3390/v13050931 - 17 May 2021

Cited by 8 | Viewed by 3441

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)

16 pages, 1622 KiB

Open AccessReview

In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?

by Ignasi Esteban, Carmen Pastor-Quiñones, Lorena Usero, Montserrat Plana, Felipe García and Lorna Leal

Viruses 2021, 13(3), 501; https://doi.org/10.3390/v13030501 - 18 Mar 2021

Cited by 16 | Viewed by 5286

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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12 pages, 601 KiB

Open AccessReview

HIV Vaccine Development: 35 Years of Experimenting in the Funding of Biomedical Research

by Stuart Z. Shapiro

Viruses 2020, 12(12), 1469; https://doi.org/10.3390/v12121469 - 19 Dec 2020

Cited by 4 | Viewed by 3383

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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13 pages, 733 KiB

Open AccessOpinion

Virus Eradication and Synthetic Biology: Changes with SARS-CoV-2?

by Jean-Nicolas Tournier and Joseph Kononchik

Viruses 2021, 13(4), 569; https://doi.org/10.3390/v13040569 - 28 Mar 2021

Cited by 2 | Viewed by 2984

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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9 pages, 571 KiB

Open AccessBrief Report

ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)

by Hervé Fleury, Sabrina Caldato, Patricia Recordon-Pinson, Patricia Thebault, Gwenda-Line Guidicelli, Mojgan Hessamfar, Philippe Morlat, Fabrice Bonnet and Jonathan Visentin

Viruses 2020, 12(11), 1256; https://doi.org/10.3390/v12111256 - 05 Nov 2020

Cited by 1 | Viewed by 2259

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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