Browsing by Author "Veldhoen, Marc"
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- CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell typesPublication . Barros, Leandro; Piontkivska, Daryna; Figueiredo-Campos, Patrícia; Fanczal, Júlia; Ribeiro, Sofia Pereira; Baptista, Marta; Ariotti, Silvia; Santos, Nuno; Amorim, Maria João; Pereira, Cristina Silva; Veldhoen, Marc; Ferreira, CristinaImmunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8+ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-β. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells.
- Correction: IgG antibodies to SARS-CoV-2 in asymptomatic blood donors at two time points in KarachiPublication . Hasan, Muhammad; Moiz, Bushra; Qaiser, Shama; Masood, Kiran Iqbal; Ghous, Zara; Hussain, Areeba; Ali, Natasha; Simas, J. Pedro; Veldhoen, Marc; Alves, Paula; Abidi, Syed Hani; Ghias, Kulsoom; Khan, Erum; Hasan, Zahra
- De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infectionPublication . Rebelo, Maria; Tang, Cong; Coelho, Ana R.; Labão-Almeida, Carlos; Schneider, Matthias M.; Tatalick, Laurie; Ruivo, Pedro; de Miranda, Marta Pires; Gomes, Andreia; Carvalho, Tânia; Walker, Matthew J.; Ausserwoeger, Hannes; Simas, J. Pedro; Veldhoen, Marc; Knowles, Tuomas P. J.; Silva, Daniel Adriano; Shoultz, David; Bernardes, Gonçalo J. L.The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.
- Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in PakistanPublication . Masood, Kiran Iqbal; Qaiser, Shama; Abidi, Syed Hani; Khan, Erum; Mahmood, Syed Faisal; Hussain, Areeba; Ghous, Zara; Imtiaz, Khekahsan; Ali, Natasha; Hasan, Muhammad; Memon, Haris Ali; Yameen, Maliha; Ali, Shiza; Baloch, Sadaf; Lakhani, Gulzar; Alves, Paula M.; Iqbal, Najeeha Talat; Ahmed, Kumail; Iqbal, Junaid; Bhutta, Zulfiqar A.; Hussain, Rabia; Rottenberg, Martin; Simas, J. Pedro; Veldhoen, Marc; Ghias, Kulsoom; Hasan, ZahraBackground: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). Methods: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell – IFN-γ activation was assessed by ELISpot. Results: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. Conclusions: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.
- Investigating the impact of prior COVID-19 on IgG antibody and interferon γ responses after BBIBP-CorV vaccination in a disease endemic population: a prospective observational studyPublication . Hasan, Zahra; Masood, Kiran Iqbal; Qaiser, Shama; Khan, Erum; Hussain, Areeba; Ghous, Zara; Khan, Unab; Yameen, Maliha; Hassan, Imran; Nasir, Muhammad Imran; Qazi, Muhammad Farrukh; Memon, Haris Ali; Ali, Shiza; Baloch, Sadaf; Bhutta, Zulfiqar A.; Veldhoen, Marc; Simas, J. Pedro; Mahmood, Syed Faisal; Ghias, Kulsoom; Hussain, RabiaBackground and Aims: COVID-19 vaccinations have reduced morbidity and mortality from the disease. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have been associated with immune protection. Seroprevalence studies revealed high immunoglobulin G (IgG) antibody levels to SARS-CoV-2 in the Pakistani population before vaccinations. We investigated the effect of BBIBP-CorV vaccination on circulating IgG antibodies and interferon (IFN)-γ from T cells measured in a cohort of healthy individuals, with respect to age, gender, and history of COVID-19. Methods: The study was conducted between April and October 2021. BBIBP-CorV vaccinated participants were followed up to 24 weeks. Antibodies to SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) were measured. IFNγ secreted by whole blood stimulation of Spike protein and extended genome antigens was determined. Results: Study participants with a history of prior COVID-19 displayed a higher magnitude of IgG antibodies to Spike and RBD. IgG seropositivity was greater in those with prior COVID-19, aged 50 years or younger and in females. At 24 weeks after vaccination, 37.4% of participants showed IFN-γ responses to SARS-CoV-2 antigens. T cell IFN-γ release was higher in those with prior COVID-19 and those aged 50 years or less. Highest IFN-γ release was observed to extended genome antigens in individuals both with and without prior COVID-19. Conclusion: We found that IgG seropositivity to both Spike and RBD was affected by prior COVID-19, age and gender. Importantly, seropositive responses persisted up to 24 weeks after vaccination. Persistence of vaccine induced IgG antibodies may be linked to the high seroprevalence observed earlier in unvaccinated individuals. Increased T cell reactivity to Spike and extended genome antigens reflects cellular activation induced by BBIBP-CorV. COVID-19 vaccination may have longer lasting immune responses in populations with a higher seroprevalence. These data inform on vaccination booster policies for high-risk groups.
- Pre-existing IgG antibodies to HCoVs NL63 and OC43 spike increased during the pandemic and after COVID-19 vaccinationPublication . Hasan, Zahra; Masood, Kiran Iqbal; Veldhoen, Marc; Qaiser, Shama; Alenquer, Marta; Akhtar, Mishgan; Balouch, Sadaf; Iqbal, Junaid; Wassan, Yaqub; Hussain, Shahneel; Feroz, Khalid; Muhammad, Sajid; Habib, Atif; Kanji, Akbar; Khan, Erum; Mian, Afsar Ali; Hussain, Rabia; Amorim, Maria Joao; Bhutta, Zulfiqar A.Preexisting immunity may be associated with increased protection against non-related pathogens such as, SARS-CoV-2. There is little information regarding endemic human coronaviruses (HCOVs) from Pakistan, which experienced a relatively low COVID-19 morbidity and mortality. We investigated antibodies to SARS-CoV-2 and HCoVs NL63 and OC43, comparing sera from prepandemic controls (PPC) period with responses in healthy controls from the pandemic (HC 2021). Further, we investigated the effect of inactivated and mRNA COVID-19 vaccinations on antibody responses to the pandemic and endemic coronaviruses. We measured IgG antibodies to Spike of SARS-CoV-2, HCoV-NL63 and HCoV-OC43 by ELISA. Serum neutralizing capacity was determined using a SARS-CoV-2 psuedotyped virus assay. Vaccinees were sampled prior to vaccination as well after 6, 12 and 24 weeks after COVID-19 inactivated (Sinovac), or mRNA (BNT162b2) vaccine administration. PPC sera showed seropositivity of 15 % to SARS-CoV-2, whilst it was 45 % in the HC 2021 group. Five percent of sera showed virus neutralizing activity in PPC whilst it was 50 % in HC 2021. IgG antibodies to Spike of NL63 and OC43 were also present in PPC; anti-NL63 was 2.9-fold, and anti-OC43 was 10.1-fold higher than to anti-SARS-CoV-2 levels. IgG antibodies to Spike SARS-CoV-2 were positively correlated with HCoV-NL63 in HC 2021, indicating recognition of shared conserved epitopes. IgG antibody levels increased during the pandemic; 2.7-fold to HCoV-NL63 and 1.9-fold to HCoV-OC43. SinoVac and BNT162b2 vaccine induced an increase in IgG antibodies to Spike SARS-CoV-2 as well as HCoV-NL63 and HCoV-OC43. Our data show that antibodies to spike protein of endemic coronaviruses were present in the prepandemic population. Antibodies to SARS-CoV-2, NL63 and OC43 were all raised during the pandemic and further enhanced after COVID-19 vaccinations. The increase in antibodies to spike of coronaviruses would contribute to protection against SARS-CoV-2.
- A rapid real-time polymerase chain reaction-based live virus microneutralization assay for detection of neutralizing antibodies against SARS-CoV-2 in blood/serumPublication . Abidi, Syed Hani; Imtiaz, Kehkashan; Kanji, Akbar; Qaiser, Shama; Khan, Erum; Iqbal, Kiran; Veldhoen, Marc; Ghias, Kulsoom; Simas, J. Pedro; Hasan, ZahraBackground Individuals recovering from COVID-19 are known to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability although they may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutralizing assays for the determination of virus-neutralizing activity in sera of individuals. Here we describe a PCR-based micro-neutralization assay that can be used to evaluate the viral neutralization titers of serum from SARS-CoV-2 infected individuals. Methods The SARS-CoV-2 strain used was isolated from a nasopharyngeal specimen of a COVID-19 case. The limiting dilution method was used to obtain a 50% tissue culture infective dose (TCID50) of Vero cells. For the micro-neutralization assay, 19 serum samples, with positive IgG titers against Spike Receptor-Binding Domain (RBD) were tested. After 24 hours, infected cells were inspected for the presence of a cytopathic effect, lysed and RNA RT-PCR conducted for SARS-CoV-2. PCR target Ct values were used to calculate percent neutralization/inhibition of SARS-CoV-2. Results Out of 19 samples, 13 samples gave 100% neutralization at all dilutions, 1 sample showed neutralization at the first dilution, 4 samples showed neutralization at lower dilutions, while one sample did not demonstrate any neutralization. The RBD ODs and neutralization potential percentages were found to be positively correlated. Conclusion We describe a rapid RT-PCR-based SARS-CoV-2 microneutralization assay for the detection of neutralizing antibodies. This can effectively be used to test the antiviral activity of serum antibodies for the investigation of both disease-driven and vaccine-induced responses.
- Seroprevalence of anti-SARS-CoV-2 antibodies in COVID-19 patients and healthy volunteers up to 6 months post disease onsetPublication . Figueiredo-Campos, Patrícia; Blankenhaus, Birte; Mota, Catarina; Gomes, Andreia; Serrano, Marta; Ariotti, Silvia; Costa, Catarina; Nunes-Cabaço, Helena; Mendes, António M.; Gaspar, Pedro; Pereira-Santos, M. Conceição; Rodrigues, Fabiana; Condeço, Jorge; Escoval, M. Antonia; Santos, Matilde; Ramirez, Mario; Melo-Cristino, José; Simas, J. Pedro; Vasconcelos, Eugenia; Afonso, Ângela; Veldhoen, MarcSARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia—COVID-19—but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of 6 months following COVID-19 onset. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff, and 198 post-COVID-19 volunteers. Anti-SARS-CoV-2 antibody responses follow a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce subsequently, the ability to detect anti-SARS-CoV-2 IgG antibodies remained robust with confirmed neutralization activity for up to 6 months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2.