Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
Antib Ther ; 5(3): 177-191, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1992090

ABSTRACT

Additional COVID-19 vaccines that are safe and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2 S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N). A single subcutaneous immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime-boost vaccination, and further improved through intramuscular heterologous prime-boost vaccination using subunit recombinant S1 protein. Priming with low dose (1 × 1010 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wild-type recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, which was sustained against Beta and Gamma SARS-CoV-2 variants. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19-based vaccines incorporating the nucleoprotein as a target antigen.

3.
Viruses ; 14(7)2022 06 30.
Article in English | MEDLINE | ID: covidwho-1917789

ABSTRACT

COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients' median age was 66 years (IQR 50-74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive/methods
4.
Vaccines (Basel) ; 10(6)2022 Jun 09.
Article in English | MEDLINE | ID: covidwho-1884445

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has severely impacted on public health, mainly on immunosuppressed patients, including solid organ transplant recipients. Vaccination represents a valuable tool for the prevention of severe SARS-CoV-2 infection, and the immunogenicity of mRNA vaccines has been evaluated in transplanted patients. In this study, we investigated the role of a third dose of the BNT162b2 vaccine in a cohort of kidney transplant recipients, analyzing both humoral and cell-mediated responses. We observed an increased immune response after the third dose of the vaccine, especially in terms of Spike-specific T cell response. The level of seroconversion remained lower than 50% even after the administration of the third dose. Mycophenolate treatment, steroid administration and age seemed to be associated with a poor immune response. In our cohort, 11/45 patients experienced a SARS-CoV-2 infection after the third vaccine dose. HLA antibodies appearance was recorded in 7 out 45 (15.5%) patients, but none of the patients developed acute renal rejection. Further studies for the evaluation of long-term immune responses are still ongoing, and the impact of a fourth dose of the vaccine will be evaluated.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-338324

ABSTRACT

Additional COVID-19 vaccines that are safe, easy to manufacture, and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2-S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N) delivered to BALB/c mice through multiple vaccine administration routes. A single subcutaneous (S.C.) immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime boost strategies, using either S.C. or intranasal (I.N.) delivery of Ad5.SARS-CoV-2-S1N, and further improved through heterologous prime boost, with traditional intramuscular (I.M.) injection, using subunit recombinant S1 protein. Priming with low dose (1×10 10 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wildtype recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, that was sustained against immune evasive Beta and Gamma SARS-CoV-2 variants, along with a long-lived plasma cell response in the bone marrow 29 weeks post vaccination. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19 based vaccines incorporating the nucleoprotein as a target antigen.

6.
Vaccines (Basel) ; 10(5)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1820440

ABSTRACT

SARS-CoV-2 still represents a global health burden, causing more than six million deaths worldwide. Moreover, the emergence of new variants has posed new issues in terms of vaccine efficacy and immunogenicity. In this study, we aimed to evaluate the neutralizing antibody response against SARS-CoV-2 variants in different cohorts of vaccinated and unvaccinated subjects. Four-fold diluted sera from SARS-CoV-2 naïve and recovered subjects vaccinated with two or three doses of the BNT162b2 vaccine were challenged against 14 SARS-CoV-2 variants, and the SARS-CoV-2 neutralizing antibody titer was measured. Results were compared with those obtained from unvaccinated COVID-19 recovered patients. Overall, a better SARS-CoV-2 NT Abs response was observed in recovered vaccinated subjects after three doses of the vaccine when compared to unvaccinated patients and vaccinated subjects with only two doses. Additionally, the lowest level of response was observed against the Omicron variant. In conclusion, third doses of BNT162b2 vaccine seems to elicit a sustained response against the large majority of variants.

7.
Transfusion ; 62(6): 1171-1176, 2022 06.
Article in English | MEDLINE | ID: covidwho-1794552

ABSTRACT

BACKGROUND: Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment. STUDY DESIGN/METHODS: In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti-SARS-CoV-2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS-CoV-2 S1/S2 and Liaison® SARS-CoV-2 TrimericS IgG assays, DiaSorin). Measures were correlated with different variables, including the time between last vaccine dose and CCP donation, and time between SARS-COV-2 infection and CCP donation. RESULTS: nAb titers against VOC Delta and Omicron were directly related to the time interval since last vaccine dose to CCP donation, but inversely related to time since COVID19 breakthrough infection. DISCUSSION: SARS-CoV-2 breakthrough infection in vaccinated in donors boosts nAb titers against VOCs Delta and Omicron, but such titers decay shortly after infection. Therefore, CCP must be collected early after vaccine breakthrough infection.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , Blood Donors , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Immunoglobulin G , Neutralization Tests , SARS-CoV-2
9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315452

ABSTRACT

BNT162b2 vaccine was introduced in Italy on 27th December 2020 and healthcare workers were rapidly vaccinated. In this study, we demonstrated that one vaccine dose was sufficient for eliciting a sustained humoral and cell-mediated response in SARS-CoV-2 experienced healthcare workers but had a lower effect in SARS-CoV-2 naïve subjects. However, 98% naïve subjects developed both neutralizing antibodies and Spike-specific T-cells after the second dose. Moreover, the antibody and T-cell responses were effective against viral variants since a partial reduction in antibody response was observed only against the South-African variant in SARS-CoV-2 naïve individuals, while the T-cell response was less affected.

10.
Transfus Apher Sci ; : 103398, 2022 Feb 16.
Article in English | MEDLINE | ID: covidwho-1683633

ABSTRACT

BACKGROUND: Test the ability of Mirasol Pathogen Reduction Technology (PRT, Terumo BCT, Lakewood Co, USA) treatment with riboflavin and ultraviolet light (R + UV) in reducing SARS-CoV-2 infectivity while maintaining blood product quality. MATERIAL AND METHODS: SARS-CoV-2 strains were isolated and titrated to prepare cell free virus for plasma units infection. The units were then under treatment with Mirasol PRT. The infectious titers were determined before and after treatment with an in house microtitration assay on Vero E6 cells. Thirty-six plasma pool bags underwent PRT treatment. RESULTS: In all the experiments, the measured titer following riboflavin and UV treatment was below the limit of detection of microtitration assay for all the different SARS-CoV-2 strains. Despite the high copies number detected by RT-PCR for each viral strain after treatment, viruses were completely inactivated and not able to infect VERO E6 cells. CONCLUSION: Riboflavin and UV light treatment effectively reduced the virus titers of human plasma to the limit of detection in tissue culture, regardless of the strain. These data suggest that pathogen reduction in blood products highlight the safety of CP therapy procedures for critically ill COVID-19 patients, while maintaining blood product quality.

11.
iScience ; 25(2): 103743, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1611783

ABSTRACT

Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.

12.
Microorganisms ; 9(12)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580570

ABSTRACT

The immunogenicity of severe acute respiratory syndrome 2 virus (SARS-CoV-2) vaccines in immunocompromised patients remains to be further explored. Here, we evaluated the immunogenicity elicited by complete vaccination with BNT162b2 vaccine in solid organ transplant recipients (SOTRs). A cohort of 110 SOTRs from Northern Italy were vaccinated with two doses of BNT162b2 mRNA vaccine and prospectively monitored at baseline and after 42 days. Both SARS-CoV-2 naïve and recovered subjects were included. Humoral response elicited by vaccination, including SARS-CoV-2 neutralizing antibodies (SARS-CoV-2 NT Abs), was evaluated; additionally, ex-vivo ELISpot assay was performed for the quantification of Spike-specific T-cell response. Results were compared with those obtained in a cohort of healthy subjects. In a subset of patients, humoral and T-cell responses against delta variant were also evaluated. Less than 20% of transplanted subjects developed a positive humoral and cell-mediated response after complete vaccination schedule. Overall, median levels of immune response elicited by vaccination were significantly lower with respect to controls in SARS-CoV-2 naïve transplant, but not in SARS-CoV-2 recovered transplanted patients. Additionally, a significant impairment of both humoral and cell-mediated response was observed in mycophenolate-treated patients. Positive delta-SARS-CoV-2 NT Abs levels were detected in almost all the SARS-CoV-2 recovered subjects but not in previously uninfected patients. Our study supports previous observations of a low level of seroconversion after vaccination in transplanted patients.

13.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295856

ABSTRACT

Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58-93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p=0.001). All analyzed patients, in whom the amount of viral RNA was sufficient for genome sequencing, results infected by the alpha variant. Antibody and T-cell responses are not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, is observed in two (6.1%) cases. This real-world data support the protective effect of BNT162b2 vaccine. A triple antigenic exposure, such as two-dose vaccine schedule in experienced subjects, may confer a higher protection.

14.
Viruses ; 13(11)2021 10 28.
Article in English | MEDLINE | ID: covidwho-1488759

ABSTRACT

We aimed to explore whether variants of SARS-CoV-2 (Chinese-derived strain (D614, lineage A), Italian strain PV10734 (D614G, lineage B.1.1) and Alpha strain (lineage B.1.1.7)) were able to infect monocytes (MN) and monocyte-derived macrophages (MDM) and whether these infected cells may, in turn, be vectors of infection. For this purpose, we designed an in vitro study following the evolution of MN and MDM infection at different time points in order to confirm whether these cells were permissive for SARS-CoV-2 replication. Finally, we investigated whether, regardless of viral replication, the persistent virus can be transferred to non-infected cells permissive for viral replication. Thus, we co-cultured the infected MN/MDM with permissive VERO E6 cells verifying the viral transmission. This is a further in vitro demonstration of the important role of MN and MDM in the dissemination of SARS-CoV-2 and evolution of the COVID-19 disease.


Subject(s)
Macrophages/virology , Monocytes/virology , SARS-CoV-2/physiology , Animals , Chlorocebus aethiops , Coculture Techniques , Coronavirus Nucleocapsid Proteins/metabolism , Humans , Macrophages/ultrastructure , Monocytes/ultrastructure , Phosphoproteins/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Virus Internalization , Virus Replication
15.
Clin Microbiol Infect ; 28(2): 301.e1-301.e8, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1474453

ABSTRACT

OBJECTIVES: To assess the humoral and cell-mediated response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by the mRNA BNT162b2 vaccine in SARS-CoV-2-experienced and -naive subjects against a reference strain and SARS-CoV-2 variants. METHODS: The humoral response (including neutralizing antibodies) and T-cell-mediated response elicited by BNT162b2 vaccine in 145 healthcare workers (both naive and positive for previous SARS-CoV-2 infection) were evaluated. In a subset of subjects, the effect of SARS-CoV-2 variants on antibody level and cell-mediated response was also investigated. RESULTS: Overall, 125/127 naive subjects (98.4%) developed both neutralizing antibodies and specific T cells after the second dose of vaccine. Moreover, the antibody and T-cell responses were effective against viral variants since SARS-CoV-2 NT Abs were still detectable in 55/68 (80.9%) and 25/29 (86.2%) naive subjects when sera were challenged against ß and δ variants, respectively. T-cell response was less affected, with no significant difference in the frequency of responders (p 0.369). Of note, two doses of vaccine were able to elicit sustained neutralizing antibody activity against all the SARS-CoV-2 variants tested in SARS-CoV-2-experienced subjects. CONCLUSIONS: BNT162b2 vaccine elicited a sustained humoral and cell-mediated response in immunocompetent subjects after two-dose administration of the vaccine, and the response seemed to be less affected by SARS-CoV-2 variants, the only exceptions being the ß and δ variants. Increased immunogenicity, also against SARS-CoV-2 variant strains, was observed in SARS-CoV-2-experienced subjects. These results suggest that triple exposure to SARS-CoV-2 antigens might be proposed as valuable strategy for vaccination campaigns.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Vaccines , Health Personnel , Humans , Vaccination , Vaccines, Synthetic
16.
Nat Commun ; 12(1): 6032, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1469967

ABSTRACT

Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58-93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p = 0.01). All analyzed patients, in whom the amount of viral RNA was sufficient for genome sequencing, results infected by the alpha variant. Antibody and T-cell responses are not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, is observed in two (6.1%) cases. This real-world data support the protective effect of BNT162b2 vaccine. A triple antigenic exposure, such as two-dose vaccine schedule in experienced subjects, may confer a higher protection.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19/diagnosis , Health Personnel/statistics & numerical data , SARS-CoV-2/pathogenicity , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Nucleic Acid Testing/statistics & numerical data , Case-Control Studies , Female , Humans , Immunization Schedule , Incidence , Male , Prospective Studies , RNA, Viral/genetics , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index
17.
Biomedicines ; 9(10)2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1438507

ABSTRACT

COVID-19 related morbidity and mortality have been often attributed to an exaggerated immune response. The role of cytokines and chemokines in COVID-19 and their contributions to illness severity are known, and thus their profiling from patient bronchoalveolar lavage (BAL) samples would help in understanding the disease progression. To date, limited studies have been performed on COVID-19 BAL samples, as the manipulation of such specimens (potentially containing live viruses) requires several laboratorial precautions, such as personnel training and special equipment, a requirement that not all laboratories can fulfil. Here, we assessed two fast and easily applicable methods (ultrafiltration and ultraviolet-C irradiation) for their impact on viral load removal or inactivation, respectively and on cytokine profiles preservation. Eight samples of BAL fluids from SARS-CoV2 patients with high viral load were tested. For both methods, complete removal was confirmed by lack of viral replication in Vero E6 cells and by RT-qPCR. Although both methods showed to remove completely the active SARS-CoV2 viral load, only UVC treatment has little or no quantitative effect on total cytokines/chemokines measurements, however cytokines profile and relative ratios are preserved or minimally altered when compared data obtained by the two different decontamination methods. Sample preparation and manipulation can greatly affect the analytical results; therefore, understanding if changes occurred after sample processing is of outmost importance for reliable data and can be useful to improve clinical practice.

18.
Int J Infect Dis ; 109: 199-202, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1385715

ABSTRACT

OBJECTIVE: The protection from SARS-CoV-2 infection induced by SARS-CoV-2 anti-S1 and anti-S2 IgG antibody positivity resulting from natural infection was evaluated. METHODS: The frequency of SARS-CoV-2 infection (as determined by virus RNA detection) was evaluated in a group of 1,460 seropositive and a control group of 8,150 seronegative healthcare workers in three Centres of Northern Italy in the period June-November 2020. Neutralizing serum titers were analyzed in seropositive subjects with or without secondary SARS-CoV-2 infection. RESULTS: During the 6-month survey, 1.78% seropositive subjects developed secondary SARS-CoV-2 infection while 6.63% seronegative controls developed primary infection (odds ratio: 0.26; 95% confidence interval: 0.17-0.38). Secondary infection was associated with low or absent serum neutralizing titer (p<0.01) and was mildly symptomatic in 45.8% cases vs 71.4% symptomatic primary infections (odds ratio: 0.34; 95% confidence interval: 0.16-0.78). CONCLUSIONS: Immunity from natural infection appears protective from secondary infection; therefore, vaccination of seronegative subjects might be prioritized.


Subject(s)
COVID-19 , Coinfection , Antibodies, Viral , Health Personnel , Humans , Incidence , Italy/epidemiology , Retrospective Studies , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL