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3.
Int J Mol Sci ; 23(21)2022 Oct 30.
Article in English | MEDLINE | ID: covidwho-2090212

ABSTRACT

Mutations in surface proteins enable emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to escape a substantial fraction of neutralizing antibodies and may thus weaken vaccine-driven immunity. To compare available vaccines and justify revaccination, rapid evaluation of antibody (Ab) responses to currently circulating SARS-CoV-2 variants of interest (VOI) and concern (VOC) is needed. Here, we developed a multiplex protein microarray-based system for rapid profiling of anti-SARS-CoV-2 Ab levels in human sera. The microarray system was validated using sera samples from SARS-CoV-2-free donors and those diagnosed with COVID-19 based on PCR and enzyme immunoassays. Microarray-based profiling of vaccinated donors revealed a substantial difference in anti-VOC Ab levels elicited by the replication-deficient adenovirus vector-base (Sputnik V) and whole-virion (CoviVac Russia COVID-19) vaccines. Whole-virion vaccine-induced Abs showed minor but statistically significant cross-reactivity with the human blood coagulation factor 1 (fibrinogen) and thrombin. However, their effects on blood clotting were negligible, according to thrombin time tests, providing evidence against the concept of pronounced cross-reactivity-related side effects of the vaccine. Importantly, all samples were collected in the pre-Omicron period but showed noticeable responses to the receptor-binding domain (RBD) of the Omicron spike protein. Thus, using the new express Ab-profiling system, we confirmed the inter-variant cross-reactivity of the anti-SARS-CoV-2 Abs and demonstrated the relative potency of the vaccines against new VOCs.


Subject(s)
Antibody Formation , COVID-19 Vaccines , Humans , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation/genetics , COVID-19/prevention & control , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Vaccination , Viral Vaccines/genetics , Viral Vaccines/pharmacology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/pharmacology , Microarray Analysis
4.
Breast Cancer Res Treat ; 195(3): 311-323, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2059914

ABSTRACT

PURPOSE: Vaccination is an essential strategy to prevent infection in the SARS-CoV-2 pandemic. However, there are concerns about vaccine efficacy and the impact of vaccination on cancer treatment. Additionally, the emergence of novel variants may affect vaccination efficacy. This multi-center, prospective, observational study investigated the efficacy and impact of vaccination against SARS-CoV-2 variants on treatment among breast cancer patients in Japan. METHODS: Patients with breast cancer scheduled to be vaccinated with the SARS-CoV-2 vaccine from May to November 2021 were prospectively enrolled (UMIN000045527). They were stratified into five groups according to their cancer treatment: no treatment, hormone therapy, anti-human epidermal growth factor receptor (HER)2 therapy, chemotherapy, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Serum samples for assessing serological responses were collected before the first vaccination and after the second vaccination. RESULTS: Eighty-five breast cancer patients were included. The overall seroconversion rate after second vaccination was 95.3% and the lowest seroconversion rate was 81.8% in the patients under chemotherapy. The overall positivity rate of neutralizing antibodies against the wild-type, α, Δ, κ, and omicron variants were 90.2%, 81.7%, 96.3%, 84.1%, and 8.5%, respectively. Among the patients under chemotherapy or CDK4/6 inhibitors, various degrees of decreased neutralizing antibody titers against SARS-CoV-2 variants were observed. Withdrawal or reduction of systemic therapy because of vaccination was observed in only one patient. CONCLUSION: Our data support SARS-CoV-2 vaccination for breast cancer patients. However, a reduction in neutralizing antibody titers was suggested during chemotherapy and CDK4/6 inhibitors, raising concerns about the impact on long-term infection prevention.


Subject(s)
Breast Neoplasms , COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , Breast Neoplasms/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Prospective Studies , SARS-CoV-2 , Vaccination , Vaccines, Inactivated , Viral Vaccines/pharmacology
5.
BMC Med ; 20(1): 347, 2022 09 16.
Article in English | MEDLINE | ID: covidwho-2029711

ABSTRACT

BACKGROUND: Heterogeneity of the population in relation to infection, COVID-19 vaccination, and host characteristics is likely reflected in the underlying SARS-CoV-2 antibody responses. METHODS: We measured IgM, IgA, and IgG levels against SARS-CoV-2 spike and nucleocapsid antigens in 1076 adults of a cohort study in Catalonia between June and November 2020 and a second time between May and July 2021. Questionnaire data and electronic health records on vaccination and COVID-19 testing were available in both periods. Data on several lifestyle, health-related, and sociodemographic characteristics were also available. RESULTS: Antibody seroreversion occurred in 35.8% of the 64 participants non-vaccinated and infected almost a year ago and was related to asymptomatic infection, age above 60 years, and smoking. Moreover, the analysis on kinetics revealed that among all responses, IgG RBD, IgA RBD, and IgG S2 decreased less within 1 year after infection. Among vaccinated, 2.1% did not present antibodies at the time of testing and approximately 1% had breakthrough infections post-vaccination. In the post-vaccination era, IgM responses and those against nucleoprotein were much less prevalent. In previously infected individuals, vaccination boosted the immune response and there was a slight but statistically significant increase in responses after a 2nd compared to the 1st dose. Infected vaccinated participants had superior antibody levels across time compared to naïve-vaccinated people. mRNA vaccines and, particularly the Spikevax, induced higher antibodies after 1st and 2nd doses compared to Vaxzevria or Janssen COVID-19 vaccines. In multivariable regression analyses, antibody responses after vaccination were predicted by the type of vaccine, infection age, sex, smoking, and mental and cardiovascular diseases. CONCLUSIONS: Our data support that infected people would benefit from vaccination. Results also indicate that hybrid immunity results in superior antibody responses and infection-naïve people would need a booster dose earlier than previously infected people. Mental diseases are associated with less efficient responses to vaccination.


Subject(s)
COVID-19 , Viral Vaccines , Antibody Formation , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines , Cohort Studies , Humans , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Middle Aged , Nucleoproteins , SARS-CoV-2 , Spain/epidemiology , Vaccination , Viral Vaccines/pharmacology
6.
Clin Transl Med ; 12(9): e1025, 2022 09.
Article in English | MEDLINE | ID: covidwho-2027333

ABSTRACT

BACKGROUND: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. METHODS: We investigated a total of 137 APs infected with SARS-CoV-2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD-, S1-, SSA/Ro- and dsDNA-specific IgG. RESULTS: While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection-induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID-19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. CONCLUSION: Our results reveal an immune mechanism that controls SARS-CoV-2-induced detrimental B cell responses and COVID-19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.


Subject(s)
COVID-19 , Viral Vaccines , B-Lymphocytes , COVID-19 Vaccines , Cytokines , Humans , Mitochondria , SARS-CoV-2 , Severity of Illness Index , Viral Vaccines/pharmacology
7.
Mikrobiyol Bul ; 56(3): 566-573, 2022 Jul.
Article in Turkish | MEDLINE | ID: covidwho-1988335

ABSTRACT

Vaccination induces the development of long-lasting immunity necessary for a sustained and essential protective antibody response. Understanding how long the humoral immune response induced by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inactivated vaccine lasts is important to create an effective immunization scheme. This study aimed to detect the first, third, sixth month concentrations and seroconversion rates of the antibodies induced by the inactivated vaccine. The study included 282 healthcare workers who were vaccinated at days 0 and 28 by the inactivated SARS-CoV-2 vaccine (3 µg/0.5ml). Anti-S-RBD-IgG (receptor binding domain) antibody concentrations and seroconversion rates were examined in vaccinated healthcare workers at the first, third and sixth months after the vaccination. MAGLUMI SARS-CoV-2 S-RBD IgG (CLIA) (Snibe Diagnostics, Chinese) kit was used for the detection of antibodies. The mean age of the healthcare workers was 38.93 ± 10.59 (min= 21-max= 64). After the administration of the second vaccine dose, the participants were found to be reactive for anti-SRBD-IgG antibodies by 98.2% and 97.8% at the first and third months, respectively,. The decrease in the mean plasma concentrations of anti-S-RBD IgG was observed as 56.7% in the cohort with only two doses of the vaccine (first month: 42.4 AU/ml versus third month: 18.2 AU/ml). In the cohort with a history of coronavirus disease 2019 (COVID-19) prior to the vaccination, the decrease was observed as 25.1% (first month: 58.29 versus third month: 43.64 AU/ml) and at a mean of 57.4 (0-90) days prior to vaccination, the decrease rate was 43.1% (first month: 55.05 AU/ml versus third month: 31.28 AU/ml), keeping more stable in participants infected at a mean of 183.1 (91-330) days prior to vaccination(a decrease of 5.2%; with 62.34 AU/ml at first and 59.08 AU/ml at third months). At the end of the sixth month, antibodies could not be detected in 16.7% of people who (n= 42) received two doses of the inactivated vaccine, and the amount of anti-S-RDB IgG decreased by an average of 52.5% compared to the third month, and by 74.8% compared to the first month. Antibody concentrations at the first, third, and sixth months after the vaccination with two doses of the inactivated SARS-CoV-2 vaccine were found to be decreased and at the sixth month, the rate of non-reactive people was 16.7%. As participants who had COVID-19 at a mean of 181 (90-330) days before the vaccination presented with a more stable antibody level, it can be concluded that a booster at months 6-12, resulting in a schedule of 0-1-6 months, is recommended for the inactive SARS-CoV-2 vaccination for effective herd immunity.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Humoral , Immunoglobulin G , SARS-CoV-2 , Vaccines, Inactivated , Viral Vaccines/pharmacology
8.
Biosensors (Basel) ; 12(8)2022 Aug 04.
Article in English | MEDLINE | ID: covidwho-1979120

ABSTRACT

To prevent the COVID-19 pandemic that threatens human health, vaccination has become a useful and necessary tool in the response to the pandemic. The vaccine not only induces antibodies in the body, but may also cause adverse effects such as fatigue, muscle pain, blood clots, and myocarditis, especially in patients with chronic disease. To reduce unnecessary vaccinations, it is becoming increasingly important to monitor the amount of anti-SARS-CoV-2 S protein antibodies prior to vaccination. A novel SH-SAW biosensor, coated with SARS-CoV-2 spike protein, can help quantify the amount of anti-SARS-CoV-2 S protein antibodies with 5 µL of finger blood within 40 s. The LoD of the spike-protein-coated SAW biosensor was determined to be 41.91 BAU/mL, and the cut-off point was determined to be 50 BAU/mL (Youden's J statistic = 0.94733). By using the SH-SAW biosensor, we found that the total anti-SARS-CoV-2 S protein antibody concentrations spiked 10-14 days after the first vaccination (p = 0.0002) and 7-9 days after the second vaccination (p = 0.0116). Furthermore, mRNA vaccines, such as Moderna or BNT, could achieve higher concentrations of total anti-SARS-CoV-2 S protein antibodies compared with adenovirus vaccine, AZ (p < 0.0001). SH-SAW sensors in vitro diagnostic systems are a simple and powerful technology to investigate the local prevalence of COVID-19.


Subject(s)
Biosensing Techniques , COVID-19 , Viral Vaccines , Antibodies, Viral , COVID-19/diagnosis , COVID-19/prevention & control , Humans , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Viral Vaccines/pharmacology
9.
N Engl J Med ; 387(6): 525-532, 2022 08 11.
Article in English | MEDLINE | ID: covidwho-1947717

ABSTRACT

BACKGROUND: Since it was first identified in early November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly and replaced the B.1.617.2 (delta) variant as the dominant variant in many countries. Data on the real-world effectiveness of vaccines against the omicron variant in children are lacking. METHODS: In a study conducted from January 21, 2022, through April 8, 2022, when the omicron variant was spreading rapidly, we analyzed data on children in Singapore who were 5 to 11 years of age. We assessed the incidences of all reported SARS-CoV-2 infections (confirmed on polymerase-chain-reaction [PCR] assay, rapid antigen testing, or both), SARS-CoV-2 infections confirmed on PCR assay, and coronavirus disease 2019 (Covid-19)-related hospitalizations among unvaccinated, partially vaccinated (≥1 day after the first dose of vaccine and up to 6 days after the second dose), and fully vaccinated children (≥7 days after the second dose). Poisson regression was used to estimate vaccine effectiveness from the incidence rate ratio of outcomes. RESULTS: A total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19-related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19-related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively. CONCLUSIONS: During a period when the omicron variant was predominant, BNT162b2 vaccination reduced the risks of SARS-CoV-2 infection and Covid-19-related hospitalization among children 5 to 11 years of age.


Subject(s)
BNT162 Vaccine , COVID-19 , SARS-CoV-2 , Vaccine Efficacy , BNT162 Vaccine/pharmacology , BNT162 Vaccine/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Child , Child, Preschool , Hospitalization/statistics & numerical data , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Singapore/epidemiology , Vaccine Efficacy/statistics & numerical data , Viral Vaccines/pharmacology , Viral Vaccines/therapeutic use
10.
Endocrine ; 78(2): 241-246, 2022 11.
Article in English | MEDLINE | ID: covidwho-1906520

ABSTRACT

The COVID-19 pandemic has posed a significant health threat globally. Timely and appropriate vaccination is a key step to reduce the morbidity and mortality from COVID-19. The clinical course of COVID-19 infection and the effects of COVID-19 vaccination are influenced by patients' health situations and involve a systemic physiological reaction. Just like an "endocrine phenotype" of COVID-19 infection, endocrine dysfunction after COVID-19 vaccination also acquired clinical concerns. In the present review, we briefly introduce the commonly available vaccines against SARS-CoV-2, summarize the influence of COVID-19 vaccines on the endocrine system, and explore the underlying pathogenic mechanisms.


Subject(s)
COVID-19 , Viral Vaccines , Humans , COVID-19 Vaccines , Pandemics/prevention & control , COVID-19/prevention & control , SARS-CoV-2 , Viral Vaccines/pharmacology , Endocrine System
11.
J Hum Lact ; 38(3): 401-406, 2022 08.
Article in English | MEDLINE | ID: covidwho-1896261

ABSTRACT

BACKGROUND: SARS-CoV-2-specific antibodies are secreted into human milk after women are vaccinated against COVID-19, which might protect the breastfed infant. Due to several reports of severe side-effects of the Oxford-AstraZeneca ChAdOx1 (AZD1222) vaccine against COVID-19, some lactating women followed a heterologous vaccination schedule consisting of the first dose of AZD1222 and a second dose of an mRNA-based vaccine. However, it is unclear whether this generates a significant SARS-CoV-2-specific antibody response in human milk. MAIN ISSUE: To quantify the SARS-CoV-2-specific antibody response in human milk of two lactating women receiving a heterologous vaccination schedules: AZD1222 and mRNA-based vaccine (Pfizer-BioNTech [BNT162b2] and Moderna [mRNA-1273]). MANAGEMENT: Both participants collected 16 samples of human milk longitudinally. SARS-CoV-2-specific Immunoglobulin A was measured using an enzyme-linked immunosorbent assay. CONCLUSION: Based on our results, it could be suggested that heterologous vaccination with AZD1222 and an mRNA-based vaccine can elicit a significant SARS-CoV-2 specific IgA response in human milk.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , Antibody Formation , BNT162 Vaccine , Breast Feeding , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Female , Humans , Lactation , Milk, Human , RNA, Messenger , SARS-CoV-2 , Viral Vaccines/pharmacology
12.
Immunohorizons ; 6(4): 275-282, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1818325

ABSTRACT

Putative subcomponent vaccines of severe acute respiratory syndrome coronavirus spike protein and ARNAX (TLR3-specific adjuvant for priming dendritic cells) were examined and compared with spike protein + Alum in a mouse BALB/c model. Survival, body weight, virus-neutralizing Ab titer in the blood, and viral titer in the lung were evaluated for prognosis markers. The infiltration degrees of eosinophils in the lung were histopathologically monitored at 10 d postinfection. The results were: (1) adjuvant was essential in vaccines to achieve a complete recovery from infection, (2) ARNAX displayed optimal body weight recovery compared with Alum, (3) ARNAX was optimal for the amelioration of eosinophilic pneumonia, and (4) the eosinophil infiltration score was not associated with the neutralizing Ab titer in the blood or viral titer in the lung. Although the pathological link between the TLR3 vaccine and lung eosinophil infiltration remains unclear, severe acute respiratory syndrome-mediated eosinophilic pneumonia can be blocked by the prior induction of dendritic cell priming by ARNAX.


Subject(s)
Pulmonary Eosinophilia , Severe acute respiratory syndrome-related coronavirus , Viral Vaccines , Adjuvants, Immunologic/pharmacology , Animals , Body Weight , Dendritic Cells , Disease Models, Animal , Mice , Pulmonary Eosinophilia/prevention & control , Toll-Like Receptor 3 , Viral Vaccines/pharmacology
13.
Bosn J Basic Med Sci ; 22(5): 833-842, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-1791623

ABSTRACT

The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-COV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to completean individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.


Subject(s)
COVID-19 Vaccines , COVID-19 , Neoplasms , Viral Vaccines , Bosnia and Herzegovina , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Humans , SARS-CoV-2 , Vaccination , Viral Vaccines/pharmacology
14.
BMC Med ; 20(1): 128, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1765453

ABSTRACT

BACKGROUND: Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. METHODS: Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Sídák's or Holm-Sídák's test. RESULTS: We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30-60 days vs. 210-270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. CONCLUSIONS: These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.


Subject(s)
COVID-19 , Viral Vaccines , Antibody Formation , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines , Humans , Immunization, Passive , Prospective Studies , SARS-CoV-2 , Viral Vaccines/pharmacology , COVID-19 Serotherapy
16.
Front Immunol ; 12: 645210, 2021.
Article in English | MEDLINE | ID: covidwho-1383856

ABSTRACT

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , Myeloid-Derived Suppressor Cells/immunology , Vaccination , Vaccinia virus/immunology , Vaccinia/immunology , Viral Vaccines/pharmacology , Animals , Injections, Intradermal , Injections, Intramuscular , Macaca fascicularis , Male , Vaccines, Attenuated/pharmacology
17.
Cell Rep ; 36(4): 109452, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1306891

ABSTRACT

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.


Subject(s)
Antibodies, Neutralizing/pharmacology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/pharmacology , Administration, Intranasal/methods , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibodies, Viral/pharmacology , Mice , Vaccination/methods , Viral Vaccines/immunology
18.
Microbiol Immunol ; 64(1): 33-51, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-1262996

ABSTRACT

The spike (S) protein of coronavirus, which binds to cellular receptors and mediates membrane fusion for cell entry, is a candidate vaccine target for blocking coronavirus infection. However, some animal studies have suggested that inadequate immunization against severe acute respiratory syndrome coronavirus (SARS-CoV) induces a lung eosinophilic immunopathology upon infection. The present study evaluated two kinds of vaccine adjuvants for use with recombinant S protein: gold nanoparticles (AuNPs), which are expected to function as both an antigen carrier and an adjuvant in immunization; and Toll-like receptor (TLR) agonists, which have previously been shown to be an effective adjuvant in an ultraviolet-inactivated SARS-CoV vaccine. All the mice immunized with more than 0.5 µg S protein without adjuvant escaped from SARS after infection with mouse-adapted SARS-CoV; however, eosinophilic infiltrations were observed in the lungs of almost all the immunized mice. The AuNP-adjuvanted protein induced a strong IgG response but failed to improve vaccine efficacy or to reduce eosinophilic infiltration because of highly allergic inflammatory responses. Whereas similar virus titers were observed in the control animals and the animals immunized with S protein with or without AuNPs, Type 1 interferon and pro-inflammatory responses were moderate in the mice treated with S protein with and without AuNPs. On the other hand, the TLR agonist-adjuvanted vaccine induced highly protective antibodies without eosinophilic infiltrations, as well as Th1/17 cytokine responses. The findings of this study will support the development of vaccines against severe pneumonia-associated coronaviruses.


Subject(s)
Adjuvants, Immunologic/pharmacology , Coronavirus Infections/prevention & control , Gold/chemistry , Immunoglobulin G/immunology , Lung/immunology , Metal Nanoparticles/chemistry , Severe Acute Respiratory Syndrome/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Analysis of Variance , Animals , Antibodies, Viral/immunology , Chlorocebus aethiops , Coronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/metabolism , Disease Models, Animal , Female , Immunization , Lung/pathology , Mice , Mice, Inbred BALB C , Recombinant Proteins/immunology , Severe acute respiratory syndrome-related coronavirus/immunology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/genetics , Toll-Like Receptors , Vaccination , Vaccines, Synthetic , Vero Cells , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Viral Vaccines/immunology , Viral Vaccines/pharmacology , Viral Vaccines/therapeutic use
19.
Eur J Pharmacol ; 896: 173930, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1139488

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , COVID-19 , Nanomedicine/methods , SARS-CoV-2/drug effects , Viral Vaccines/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Drug Development , Humans
20.
Expert Opin Drug Discov ; 16(2): 115-117, 2021 02.
Article in English | MEDLINE | ID: covidwho-1066185

ABSTRACT

Introduction: The COVID-19 pandemic has catalyzed the production of potential antivirals and vaccines from research organizations across the globe. The initial step for all drug discovery models is the identification of suitable targets. One approach organizations may take to tackle this involves issuing raw data publicly for collaboration with other organizations in order to spark discussion, collectively experiment and stay up to date with advances in scientific knowledge. Areas covered: Numerous organizations have released genomic data, amongst other tools, for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and this has led to the development of growing datasets of knowledge for continued collaboration amongst different scientific communities. A different technique employs a more closed, market-driven method in order to stay ahead financially in the race for developing a suitable antiviral or vaccine. The latter allows sustained motivation for company ambitions and progress has been made toward clinical trials for potential drugs. Expert opinion: A case can be made for both open and closed drug discovery models; however, due to the rapidly evolving nature of this deadly virus, organizations should collate their research and support one another to ensure satisfactory treatment can be approved in a timely manner.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Drug Discovery/organization & administration , SARS-CoV-2 , Viral Vaccines/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Clinical Trials as Topic , Drug Discovery/economics , Drug Discovery/methods , Humans , International Cooperation , SARS-CoV-2/drug effects , SARS-CoV-2/genetics
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