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1.
Cell Rep Med ; 4(6): 101084, 2023 06 20.
Article in English | MEDLINE | ID: covidwho-2327715

ABSTRACT

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.


Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , COVID-19 Vaccines , COVID-19/prevention & control , Immunity, Cellular
2.
Topics in Antiviral Medicine ; 31(2):379, 2023.
Article in English | EMBASE | ID: covidwho-2319830

ABSTRACT

Background: Wastewater represents a broad, immediate, and unbiased accounting of the pathgens in the population. We aimed to develop methods to track HIV in wastewater utilizing a viral detection pipeline adapted from platforms developed to track SARS-COV-2. Method(s): We used samples from 6 wastewater treatment plants in the Houston area. We focused on regions of higher prevalence and lower prevalence. First, employing wastewater processing and nucleic acid extraction methods described by our group to detect SARS-COV-2, we tested a single high and low prevalence site in triplicate with all 3 primer sets. nucleic acid extracts from HIV and SIV cell culture supernatants were used as controls. Next, in subsequent samples, RT-PCR reactions with detections were subjected to gel electrophoresis to determine the amplified product sizes. To further confirm HIV detection, we sequenced the RT-PCR products and compared the proportion of reads which mapped to the expected amplified product. In a later set of studies, we fractionated samples into supernatant and pellet. We further tested HIV presence by performing whole virome sequencing on the extracts from some samples that produced detections and mapped reads to published genomes. A crAssphage genome was used as a negative control. Result(s): Samples from all sites resulted in signal detection at least once. Only reactions with gag and pol primers appeared to amplify the expected product. Products from the HIV positive control mapped almost exclusively to the HIV genome (97-100% of reads), with a fraction of reads from the SIV negative control doing the same (16-18% of reads). The ltr and pol products did not map the HIV genome while gag products did (34-44% of reads). Among the fractionated sample, in total, 6 supernatant fractions produced no detection compared to 7 of 8 pellet fractions. The whole virome sequencing produced reads that mapped to the HIV genome with at least 8X depth coverage. The sample with the lowest Ct detection (26) yielded HIV coverage several logs greater than those samples with higher Ct detection (37). Reads from all samples mapped to at least 20% of the HIV genome. Conclusion(s): This work provides the first evidence that HIV can be detected in municipal wastewater systems and has the potential to be developed into a new public health tool.

3.
Topics in Antiviral Medicine ; 31(2):117, 2023.
Article in English | EMBASE | ID: covidwho-2314619

ABSTRACT

Background: Individuals living with HIV are at increased risk of morbidity and mortality from COVID-19. Furthermore, SARS-CoV-2 infection in immunocompromised HIV infected individuals poses a risk to prolonged infection and viral shedding and the emergence of new variants of concern (VOCs). Using the SIV macaque model for AIDS, we are investigating the hypothesis that immune dysfunction during HIV infection will prolong SARSCoV- 2 viral infection, promote enhanced COVID-19 disease, and accelerate viral evolution. Here, we report the impact of SIV-CoV-2 co-infection on immune responses and pathogenesis. Method(s): Eight female rhesus macaques (aged 7-15 years, 5.5-9.9kg) were infected with SIVmac251 via low dose intravaginal challenge and then inoculated with 6.5x105 TCID50/mL SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV infection via combined intranasal and intratracheal routes. Blood, bronchoalveolar lavage (BAL), stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI) to measure immune responses and viremia. ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Result(s): Three days post-SARS-CoV-2 infection, we observed a transient decrease in CD4 counts, but there were no changes in clinical symptoms or plasma SIV viral loads. However, SARS-CoV-2 replication persisted in the upper respiratory tract, but not the lower respiratory tract. In addition, SARS-CoV-2 IgG seroconversion was delayed and antigen-specific T-cell responses were dampened. Notably, viral RNA levels in nasal swabs were significantly higher 7-14 DPI in SIV+ compared to previously published results using the same SARS-CoV-2 challenge virus in SIV- rhesus (PMCID: PMC8462335, PMC8829873). In addition, SIV/CoV-2 co-infected animals exhibited elevated levels of myeloperoxidase (MPO), a marker of neutrophil activation and increased lung inflammation. Conclusion(s): Here we provide evidence for the utility of the rhesus macaque in modeling human HIV-SARS-CoV-2 co-infection. Our results suggest that immunosuppression during SIV infection impairs de novo generation of anti-SARS-CoV-2 immunity, that may contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine if SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques.

4.
Kidney International Reports ; 8(3 Supplement):S395, 2023.
Article in English | EMBASE | ID: covidwho-2276922

ABSTRACT

Introduction: Generating adequate cellular and humoral responses are essential principle of vaccination. Immune system of renal transplant recipient remained compromised and speculated to less likely to develop antibody after vaccination. SARS-CoV-2 neutralizing antibody after anti-SARS-CoV-2 vaccination is required for the protection from subsequent viral infection. During COVID-19 disease, anti-SARS-CoV-2 specific antibody formation was correlated with the inflammatory cytokines level. Although, there is limited informations about serum cytokines and antibody formation after COVAXINTM, COVISHIELDTM vaccination in RTRs. Therefore, in the current study, we have evaluated the inflammatory cytokines response and anti-SARS-CoV-2 specific antibody formation in renal transplant recipient. Method(s): In this study, we have recruited 171 live-related renal transplant recipients vaccinated with two doses of either COVAXINTM (whole inactivated virus-based vaccine) or COVISHIELDTM (Simian adenovirus containing full-length spike protein-based vaccine). A 5 ml blood sample was collected after two weeks of 2nd dose of vaccination. The serum was separated and stored at -200C till the analysis. Anti-SARS-CoV-2 spike protein-specific IgG antibody titer was determined by chemiluminescent microparticle immunoassay methods and Cytokines IL-10, TGF-beta, IFN-gamma, IL-6 were measured by the ELISA techniques. Result(s): The overall anti-SARS-CoV-2 spike protein specific seroconversion after vaccination was observed in 149/171(87.13%) of RTRs with median IgG titer in seroconversion group 1191.90 (IQR, 398.70-2652.45) au/ml. The median and interquartile serum cytokines IL-10 level in seroconversion (n=149) vs non-seroconversion (n=22) group was 88.89 (IQR, 55.5-125.92) vs 92.59 (IQR, 48.14-148.14) pg/ml. The median TGF-beta level in seroconversion vs non-seroconversion group was 692.10 (IQR, 446.05-927.63) vs 1001.31 (IQR, 813.15-1125.65) pg/ml. The median IL-6 level in seroconversion vs non-seroconversion group was 46.66 (33.3-66.66) vs 28.33 (16.66-34.16) pg/ml. The median IFN-gamma level in seroconversion vs non-seroconversion group was 98.0 (IQR, 57.40-111.60) vs 50.0 (IQR, 30.55-52.55) pg/ml. The cytokines IL-6 and IFN-gamma level was positively correlated with anti-SARS-CoV-2 specific protein antibody titer (r=0.192;p=0.012), IFN-gamma (r=0.188;p=0.014). TGF-beta and IL-10 were negatively correlated with anti-SARS-CoV-2 specific protein antibody titer. For IL-10 (r=-0.065;p=0.39), for TGF-beta (r=-0.246;p=0.002). Further IFN-gamma was negatively correlated with TGF-beta (r=-0.268;p<0.001). Conclusion(s): Higher pro-inflammatory cytokines (IL-6, IFN-gamma) levels were associated with anti-SARS-CoV-2 spike protein-specific seroconversion, whereas higher anti-inflammatory cytokines IL-10 and TGF-beta were negatively associated with seroconversion after vaccination in renal transplant recipients. No conflict of interestCopyright © 2023

5.
Bulletin of Russian State Medical University ; 2023(1):4-11, 2023.
Article in English | EMBASE | ID: covidwho-2275269

ABSTRACT

Technological versatility and the humoral and cellular immune response induction capacity have conditioned wide spread of adenoviral vectors as vaccine and gene therapy drugs. However, vaccination with Sputnik V made a significant portion of the population immune to the types 5 and 26 (Ad5 and Ad26) recombinant human adenovirus vectors, which are some of the most frequently used bases for candidate vaccines. Today, vaccine designers tend to select alternative adenovirus serotypes as platforms to develop vaccines against new pathogens on. A good example is simian adenovirus type 25 (SAd25), which belongs to subgroup E. It is genetically distant from Ad5 and exhibits extremely low seroprevalence in human beings, which makes it an appealing alternative vaccine vector. The purpose of this work was to design and study a new vaccine platform based on simian adenovirus type 25. We relied on the advanced methods of molecular biology and virology to construct and make recombinant adenoviruses;the phylogenetic analysis in the context of this study was enabled with bioinformatic methods. The resulting recombinant adenoviral vector can effectively replicate itself in the HEK293 cell line (human embryonic kidney cells). This work substantiates the expediency of further investigation into the SAd25 vector as a platform for development of the prevention vaccines against various infectious diseases.Copyright © 2023 Pirogov Russian National Research Medical University. All rights reserved.

6.
British Journal of Dermatology ; 187(Supplement 1):187, 2022.
Article in English | EMBASE | ID: covidwho-2271205

ABSTRACT

We present a literature review of dermatology features in historical pandemics. A pandemic is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and affecting a large number of people. Smallpox was the first documented pandemic, around 10 000 BC, spread by the inhalation of airborne droplets. A few days after an initial high fever, headache and fatigue, a mucocutaneous maculopapular eruption appeared, which then developed pustules and erosions. The last outbreak occurred in the USA in 1949. Smallpox was eradicated in 1980, following a vaccination programme. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), an ongoing global pandemic. The earliest documentations were 3300 years ago. In 2020, the World Health Organization (WHO) provisionally estimated 1.5 million deaths globally. Most commonly affecting the lungs, cutaneous TB may present with inflammatory papules, plaques, suppurative nodules and chronic ulcers. Requiring long, complex antibiotic regimens, multidrug resistant TB is an increasing problem. Now extremely rare, yet still with recent outbreaks in 2021 in Madagascar, bubonic plague arrived in Europe in 1346 causing 75-200 million deaths. It is caused by the bacterium Yersinia pestis, transmitted through fleas that have fed on infected rodents. Clinical features include papules, pustules, ulcers and eschars, tender lymphadenopathy and systemic symptoms, and it responds to antibiotics. Syphilis, caused by the bacterium Treponema pallidum, is sexually transmitted. The first known outbreak was during warfare in 1494-5 in Naples, Italy. In 2020, the WHO estimated that, globally, seven million people had new infections. Primary syphilis typically produces a painless, genital ulcer (or chancre). Secondary syphilis presents with a nonitchy, maculopapular erythema over the trunk, palms and soles. Early recognition and antibiotic treatment usually lead to good outcomes. Estimated by the WHO to affect 37.7 million people in 2020, HIV is thought to have mutated from simian immunodeficiency virus by the 1960s in sub-Saharan Africa, spreading to the Caribbean and USA by the late 1960s. Initial symptoms include a fever, headache and lymphadenopathy. Dermatological features are common, including opportunistic cutaneous infections, nonspecific exanthemas, seborrhoeic dermatitis and Kaposi sarcoma. Advances in antiretroviral therapies mean people with HIV can have an excellent prognosis, although the WHO estimated in 2020 that more than 200 000 people with HIV died from concomitant TB. Since 2019, COVID-19 has had a considerable global impact on healthcare. With more than 300 million cases and 5.5 million deaths to date, some services have been overwhelmed owing to large case numbers, variable vaccine uptake, workplace changes to reduce transmission and staff shortages. Cutaneous features include perniosis, urticarial, purpuric, vesicular or maculopapular eruptions. Pandemics throughout history have been repeatedly shown to present with an element of skin involvement. We can utilize this to promote education and early recognition of these features, to facilitate diagnosis and raise awareness of the potential complications of serious diseases.

7.
Sociedad y Ambiente ; 24, 2021.
Article in Spanish | CAB Abstracts | ID: covidwho-2253841

ABSTRACT

The possession of exotic animals as pets is a social practice that has become more visible in Mexico in recent years, so it is interesting to understand its environmental and social implications and those related to human health. The present study aims to identify the main species of exotic animals kept as pets and the zoonotic diseases reported in these species. We analyzed official figures of seizures of exotic fauna in Mexico and reviewed specialized literature on zoonotic diseases documented in Mexico in these species. We identified zoonoses in species of fauna that can be acquired legally and illegally in the country, reported in environments in which animals coexist with other species and are in direct contact with people, which represents an important factor in the spread and propensity of this type of disease. We conclude that the sanitary regulation of wildlife markets, the monitoring and studying microorganisms associated with wildlife are valuable strategies to prevent the emergence of zoonoses.

8.
Pathogens ; 10(10)2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1516657

ABSTRACT

The most recent emerging infectious diseases originated in animals, mainly in wildlife reservoirs. Mutations and recombination events mediate pathogen jumps between host species. The close phylogenetic relationship between humans and non-human primates allows the transmission of pathogens between these species. These pathogens cause severe impacts on public health and impair the conservation of habituated or non-habituated wild-living apes. Constant exposure of great apes to human actions such as hunting, deforestation, the opening of roads, and tourism, for example, contributes to increased interaction between humans and great apes. In spite of several studies emphasizing the risks of pathogen transmission between animals and humans, outbreaks of the reverse transmission of infectious agents threatening wildlife still occur on the African continent. In this context, measures to prevent the emergence of new diseases and conservation of primate species must be based on the One Health concept; that is, they must also ensure the monitoring of the environment and involve political and social aspects. In this article, we review and discuss the anthropological aspects of the transmission of diseases between people and wild primates and discuss new anthropozoonotic diseases in great apes in Africa from studies published between 2016 and 2020. We conclude that the health of great apes also depends on monitoring the health of human populations that interact with these individuals.

9.
American Journal of Transplantation ; 22(Supplement 3):572, 2022.
Article in English | EMBASE | ID: covidwho-2063393

ABSTRACT

Purpose: To study the clinical application of metagenomic next-generation sequencing (mNGS) in the detection of viral infections in kidney transplant recipients (KTRs) during the COVID-19 pandemic. Method(s): Using mNGS techniques, 50 human fluid samples of KTRs were detected in Henan Province People's Hospital between May 2020 to May 2021, including 20 bronchoalveolar lavage fluid (BALF) samples, 21 urine samples and 9 blood samples. The detected nucleic acid sequences were compared and analyzed with the existing viral nucleic acid sequences in the database, and the virus infection spectrum of KTRs was drawn. Result(s): The viral nucleic acids of 15 types of viruses were detected in 96.00% (48/50) of the samples, of which 11 types of viruses were in BALF (95.00%, 19/20), and the dominant viruses were torque teno virus (TTV) (65.00%;13/20), cytomegalovirus (CMV) (45.00%;9/20) and human alphaherpesvirus 1 (25.00%;5/20). 12 viruses (95.24%, 20/21) were detected in the urine, and the dominant viruses were TTV (52.38%;11/21), JC polyomavirus (52.38%;11/21), BK polyomavirus (42.86%;9/21), CMV (33.33%;7/21) and human betaherpesvirus 6B (28.57%;6/21). 7 viruses were detected in the blood (100.00%, 9/9), and the dominant virus was TTV (100.00%;9/9). Four rare viruses were detected in BALF and urine, including WU polyomavirus, primate bocaparvovirus 1, simian virus 12, and volepox virus. Further analysis showed that TTV infection with high reads indicated a higher risk of acute rejection (P<0.05). Conclusion(s): mNGS detection reveals the rich virus spectrum of infected persons after kidney transplantation, and improves the detection rate of rare viruses. TTV may be a new biomarker for predicting rejection. (Figure Presented).

10.
Trends Microbiol ; 30(10): 948-958, 2022 10.
Article in English | MEDLINE | ID: covidwho-2036564

ABSTRACT

'Infodemia' is a portmanteau between 'information' and 'epidemics', referring to wide and rapid accumulation and dissemination of information, misinformation, and disinformation about a given subject, such as a disease. As facts, rumors and fears mix and disperse, the misinfodemic creates loud background noise, preventing the general public from discerning between accurate and false information. We compared and contrasted key elements of the AIDS and COVID-19 misinfodemics, to identify common features, and, based on experience with the AIDS pandemic, recommend actions to control and reverse the SARS-CoV-2 misinfodemic that contributed to erode the trust between the public and scientists and governments and has created barriers to control of COVID-19. As pandemics emerge and evolve, providing robust responses to future misinfodemics must be a priority for society and public health.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , COVID-19/epidemiology , Communication , Humans , Pandemics/prevention & control , Public Health , SARS-CoV-2
11.
European Heart Journal, Supplement ; 24(SUPPL C):C207-C208, 2022.
Article in English | EMBASE | ID: covidwho-1915570

ABSTRACT

Il SARS-CoV2 è trasmesso tra gli umani attraverso particelle respiratorie e l'infezione può determinare un largo spettro di manifestazioni cliniche. Precedenti studi hanno dimostrato il ruolo centrale dell'immunità cellulo-mediata nel limitare la gravità delle infezioni da virus respiratori. I linfociti T-helper CD4+ sono coinvolti in funzioni di coordinazione e regolazione dell'immunità anti-virale: determinano lo sviluppo di anticorpi neutralizzanti ad alta affinità e la differenziazione dei centri germinali a cellule B in cellule della memoria secernenti anticorpi con lunga vita. Nessun dubbio sul ruolo cruciale della risposta a cellule T durante l'infezione da SARS-CoV2 o dopo la vaccinazione. Descriviamo il caso di un paziente di 39 anni, vaccinato con ChAdOx1-S. Dopo due settimane il paziente accusava dispnea e febbricola. Il test molecolare per SARS-CoV2 era negativo;agli esami ematici la PCR era aumentata. La TC del torace escludeva embolia polmonare e rivelava pattern a vetro smerigliato bilaterale, come da flogisi. All'ecocardiogramma i parametri erano nella norma. L'ECG mostrava tachicardia sinusale. Il paziente veniva dimesso dal PS con terapia cortisonica. Una settimana dopo i sintomi peggiooravano. Una nuova TC torace mostrava difetti di opacizzazione di rami secondari dell'arteria polmonare ed aspetto bilaterale a vetro smerigliato. Si iniziava terapia con EBPM ed antibiotici a largo spettro. Il test molecolare e la sierologia per SARS-CoV2 erano negativi. Negativi i test per Mycoplasma, Chlamydia, Legionella e CMV DNA. L'emocromo mostrava ridotti linfociti (6,8%) con neutrofilia relativa (90,4%), ma normale valore dei bianchi. La TC-HR mostrava aspetto “crazy paving” bilaterale suggestivo per infezione virale o micotica (pattern come da infezione da Pneumocystis Jiroveci). Il test per HIV aveva esito positivo;alla tipizzazione linfocitaria ridotti i livelli di linfociti T-Helper (CD3+/CD4+) e rapporto CD3+/CD4+ 0%. Per il rapido deterioramento del quadro clinico il paziente veniva trasferito in terapia intensiva. Dopo 30 giorni dalla diagnosi di AIDS il paziente giungeva ad exitus. Il ruolo dei linfociti T nello sviluppo di anticorpi neutralizzanti e di cellule della memoria durante l'infezione da SARS-CoV2 è la chiave nella strategia di vaccinazione per ridurre il dilagare della pandemia, tuttavia nel nostro paziente questo meccanismo non ha funzionato rivelando il deficit del suo sistema immunitario da una latente infezione da HIV. (Figure Presented).

12.
European Heart Journal, Supplement ; 24(SUPPL C):C133-C134, 2022.
Article in English | EMBASE | ID: covidwho-1915558

ABSTRACT

Case Report: A 61-year-old man, smoker and family history of cardiovascular diseases, started oral antibiotic therapy with amoxicillin / clavulanic acid following the appearance of a dental abscess. About 30 minutes after taking the antibiotic, he complained of widespread erythema in the limbs, followed by intense itching and dyspnea. Upon arrival of the medical staff, IV cortisone and antihistamine therapy was performed with gradual and progressive resolution of the symptoms. Despite the doctors' invitation, the patient refused access to the emergency room for fear of a possible hospital infection with SARS-CoV-2. Almost two months later, due to the onset of exertional dyspnea, he is persuaded to go to the hospital for further tests. The ECG showed signs of diffuse anterolateral necrosis (Figure 1). Echocardiography showed severe left ventricular dysfunction (FE 35%) with extensive akinesia of the mid-distal SIV, apex, and anterior mid-distal wall. Myocardiocytolysis indices were negative and allergy tests positive for beta-lactam antibiotics. Subsequently he underwent coronary angiography which showed proximal occlusion of an intermediate branch (Figure 2) treated with angioplasty and drug stent release. Cardiac MRI was then performed with evidence of a large area of ischemic necrosis (subendocardial / transmural) of the antero-septal, anterior and anterolateral wall with FE 35% (Figure 3). Comment: Kounis syndrome is a clinical emergency characterized by the appearance of an acute coronary syndrome during an anaphylactic-type reaction. A correct diagnosis is of fundamental importance to limit the extent of myocardial damage as much as possible. In Kounis type 2, the mediators of the allergic reaction can cause not only vasospasm but also the activation of metalloproteases that induce the degradation of collagen with consequent rupture of pre-existing atheromatous plaques, as in our patient. Failure to perform an ECG during first aid leaves doubts about the possible allergic genesis of the episode, which however cannot be excluded with certainty. We have decided to report this clinical case to emphasize the importance of always taking into consideration the possibility of being compared with a case of Kounis when assisting a patient with an anaphylactic type reaction. (Figure Presented).

14.
Virol Sin ; 36(5): 1113-1123, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1439763

ABSTRACT

SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines. However, the thermal instability and pre-existing immunity have limited its wide applications. To circumvent these obstacles, we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine (Sad23L-nCoV-S-CaP) by generating a calcium phosphate mineral exterior (CaP) based on Sad23L vector carrying the full-length gene of SARS-CoV-2 spike protein (S) under physiological condition. This Sad23L-nCoV-S-CaP vaccine was examined for its characteristics of structure, thermostability, immunogenicity and avoiding the problem of preexisting immunity. In thermostability test, Sad23L-nCoV-S-CaP could be stored at 4 °C for over 45 days, 26 °C for more than 8 days and 37 °C for approximately 2 days. Furthermore, Sad23L-nCoV-S-CaP induced higher level of S-specific antibody and T cell responses, and was not affected by the pre-existing anti-Sad23L immunity, suggesting it could be used as boosting immunization on Sad23L-nCoV-S priming vaccination. The boosting with Sad23L-nCoV-S-CaP vaccine induced high titers of 105.01 anti-S1, 104.77 anti-S2 binding antibody, 103.04 pseudovirus neutralizing antibody (IC50), and robust T-cell response of IFN-γ (1466.16 SFCs/106 cells) to S peptides, respectively. In summary, the self-biomineralization of the COVID-19 vaccine Sad23L-nCoV-S-CaP improved vaccine efficacy, which could be used in prime-boost regimen for prevention of SARS-CoV-2 infection in humans.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adenoviridae/genetics , Animals , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Vaccine Efficacy
15.
Emerg Microbes Infect ; 10(1): 1002-1015, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1231006

ABSTRACT

ABSTRACTCOVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization, Secondary , SARS-CoV-2/immunology , Adenoviridae/genetics , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/adverse effects , Female , Genetic Vectors , HEK293 Cells , Humans , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes/immunology
16.
Pathogens ; 9(4)2020 Apr 20.
Article in English | MEDLINE | ID: covidwho-88358

ABSTRACT

Emerging and re-emerging viral diseases are of great public health concern. The recent emergence of Severe Acute Respiratory Syndrome (SARS) related coronavirus (SARS-CoV-2) in December 2019 in China, which causes COVID-19 disease in humans, and its current spread to several countries, leading to the first pandemic in history to be caused by a coronavirus, highlights the significance of zoonotic viral diseases. Rift Valley fever, rabies, West Nile, chikungunya, dengue, yellow fever, Crimean-Congo hemorrhagic fever, Ebola, and influenza viruses among many other viruses have been reported from different African countries. The paucity of information, lack of knowledge, limited resources, and climate change, coupled with cultural traditions make the African continent a hotspot for vector-borne and zoonotic viral diseases, which may spread globally. Currently, there is no information available on the status of virus diseases in Africa. This systematic review highlights the available information about viral diseases, including zoonotic and vector-borne diseases, reported in Africa. The findings will help us understand the trend of emerging and re-emerging virus diseases within the African continent. The findings recommend active surveillance of viral diseases and strict implementation of One Health measures in Africa to improve human public health and reduce the possibility of potential pandemics due to zoonotic viruses.

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