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1.
J Int Med Res ; 50(3): 3000605221086155, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1753017

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 220 million individuals worldwide, and has been shown to cause increased disease severity and mortality in patients with active cancer versus healthy individuals. Vaccination is important in reducing COVID-19-associated morbidity and mortality. Thus, the aim of this article was to review the existing knowledge on effectiveness, immunogenicity and safety of COVID-19 vaccines in patients with cancer. Fifty-four articles were included following a search of PubMed and Google Scholar databases for studies published between January 2020 and September 2021 that investigated humoral and cell-mediated immune responses following COVID-19 vaccination in patients with cancer. Immunogenicity of vaccines was found to be lower in patients with cancer versus healthy individuals, and humoral immune responses were inferior in those with haematological versus solid cancers. Patient-, disease-, and treatment-related factors associated with poorer vaccine responses should be identified and corrected or mitigated when possible. Consideration should be given to offering patients with cancer second doses of COVID vaccine at shorter intervals than in healthy individuals. Patients with cancer warrant a third vaccine dose and must be prioritized in vaccination schedules. Vaccine adverse effect profiles are comparable between patients with cancer and healthy individuals.


Subject(s)
COVID-19 , Neoplasms , Viral Vaccines , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Neoplasms/complications , SARS-CoV-2 , Vaccination , Viral Vaccines/adverse effects
6.
Nat Commun ; 12(1): 4636, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1347938

ABSTRACT

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Chikungunya Fever/immunology , Chikungunya virus/immunology , Viral Vaccines/immunology , Adolescent , Adult , Chikungunya Fever/prevention & control , Chikungunya Fever/virology , Chikungunya virus/classification , Chikungunya virus/physiology , Cytokines/immunology , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Fatigue/chemically induced , Female , Headache/chemically induced , Humans , Immunoglobulin G/immunology , Injections, Intramuscular , Male , Middle Aged , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vaccination/methods , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
7.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266401

ABSTRACT

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.


Subject(s)
COVID-19 Vaccines , Neoplasms/therapy , RNA, Messenger , SARS-CoV-2/immunology , Viral Vaccines , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/therapeutic use , Drug Stability , Humans , Influenza, Human/epidemiology , Influenza, Human/immunology , Influenza, Human/prevention & control , Neoplasms/epidemiology , Neoplasms/immunology , Pandemics , RNA Stability/physiology , RNA, Messenger/administration & dosage , RNA, Messenger/adverse effects , RNA, Messenger/chemistry , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccination/methods , Viral Vaccines/adverse effects , Viral Vaccines/chemistry , Viral Vaccines/genetics
8.
Asian Pac J Allergy Immunol ; 38(3): 150-161, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1231595

ABSTRACT

SARS-CoV-2 had already killed more than 400,000 patients around the world according to data on 7 June 2020. Bacillus Calmette-Guérin (BCG) vaccine is developed from live-attenuated Mycobacterium bovis, which is a microorganism found in a cow. Discovered by Dr. Albert Calmette and Camille Guérin since 1921, the BCG has served as a protection against tuberculosis and its complications. It is noticeable that countries which use mandatory BCG vaccination approach had lower COVID-19 infection and death rate. Current review aims to clarify this issue through epidemiological illustration of correlation between national BCG immunization and COVID-19 mortality, in addition to biological background of BCG-induced immunity Epidemiological data shows that universal BCG policy countries have lower median mortality rate compare to countries with past universal BCG policy and non-mass immunization BCG. (18 May 2020). Still, the links between BCG vaccination and better COVID-19 situation in certain countries are unclear, and more data on actual infection rate using SAR-CoV-2 antibody testing in large population sample is crucial for disease spreading comparison. Two immunological mechanisms, heterologous effects of adaptive immunity and trained innate immunity which induced by BCG vaccination, may explain host tolerance against COVID-19 infection, however, there is no direct evidence to support this biological background. Clinical trials related to BCG vaccination against COVID-19 are under investigation. Without a strong evidence, BCG must not be recommended for COVID-19 prevention, although, this should not be absolute contraindication. Risk of local and systemic complications from the vaccine should be informed to individual, who request BCG immunization.


Subject(s)
BCG Vaccine/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccination , Viral Vaccines/administration & dosage , Adaptive Immunity , BCG Vaccine/adverse effects , BCG Vaccine/immunology , COVID-19 , COVID-19 Vaccines , Cause of Death , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Immunity, Innate , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , Vaccination/adverse effects , Viral Vaccines/adverse effects , Viral Vaccines/immunology
10.
Curr Opin Neurol ; 34(3): 322-328, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1132693

ABSTRACT

PURPOSE OF REVIEW: This review focuses on new evidence supporting the global immunization strategy for multiple sclerosis (MS) patients receiving disease-modifying drugs (DMDs), including the recently available vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RECENT FINDINGS: New data strengthen the evidence against a causal link between MS and vaccination. Recent consensus statements agree on the need to start vaccination early. Timings for vaccine administration should be adjusted to ensure safety and optimize vaccine responses, given the potential interference of DMDs. Patients treated with Ocrelizumab (and potentially other B-cell depleting therapies) are at risk of diminished immunogenicity to vaccines. This has relevant implications for the upcoming vaccination against SARS-CoV-2. SUMMARY: An early assessment and immunization of MS patients allows optimizing vaccine responses and avoiding potential interference with treatment plans. Vaccinations are safe and effective but some specific considerations should be followed when vaccinating before, during, and after receiving immunotherapy. A time-window for vaccination taking into account the kinetics of B cell repopulation could potentially improve vaccine responses. Further understanding of SARS-CoV-2 vaccine response dynamics in MS patients under specific therapies will be key for defining the best vaccination strategy.


Subject(s)
Antirheumatic Agents/therapeutic use , Immunization Programs/organization & administration , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Antirheumatic Agents/adverse effects , COVID-19 Vaccines/therapeutic use , Humans , Immunotherapy/adverse effects , Immunotherapy/methods , Vaccination , Viral Vaccines/adverse effects , Viral Vaccines/immunology
11.
Nature ; 586(7830): 594-599, 2020 10.
Article in English | MEDLINE | ID: covidwho-1091471

ABSTRACT

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 µg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-µg dose) to 3.5-fold (50-µg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.


Subject(s)
Antibodies, Viral/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Th1 Cells/immunology , Viral Vaccines/immunology , Adult , Antibodies, Neutralizing/immunology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/prevention & control , Cytokines/immunology , Female , Germany , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Pandemics , Th1 Cells/cytology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
16.
Nature ; 586(7830): 516-527, 2020 10.
Article in English | MEDLINE | ID: covidwho-982728

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.


Subject(s)
Coronavirus Infections , Drug Development , Pandemics , Pneumonia, Viral , Viral Vaccines , Animals , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Drug Industry , Humans , Immunity, Mucosal , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Viral Vaccines/adverse effects , Viral Vaccines/immunology , Viral Vaccines/supply & distribution
17.
Lancet ; 396(10249): 467-478, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-981752

ABSTRACT

BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/adverse effects , Viral Vaccines/immunology , Acetaminophen/therapeutic use , Adenoviruses, Simian/genetics , Adult , Analgesics, Non-Narcotic/therapeutic use , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Female , Genetic Vectors/administration & dosage , Humans , Immunization, Secondary , Immunoglobulin G/blood , Male , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Single-Blind Method , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , United Kingdom , Viral Vaccines/administration & dosage
18.
Lancet ; 396(10255): 887-897, 2020 09 26.
Article in English | MEDLINE | ID: covidwho-974769

ABSTRACT

BACKGROUND: We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine. METHODS: We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers (men and women) aged 18-60 years to both studies. In phase 1 of each study, we administered intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21. Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (T-cell responses and interferon-γ concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875. FINDINGS: Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most adverse events were mild and no serious adverse events were detected. All participants produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14 703 with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised formulation. INTERPRETATION: The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19. FUNDING: Ministry of Health of the Russian Federation.


Subject(s)
Coronavirus Infections/prevention & control , Immunization, Secondary , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adenoviridae , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G/blood , Injections, Intramuscular , Male , Russia , SARS-CoV-2 , Viral Vaccines/adverse effects , Young Adult
19.
N Engl J Med ; 383(20): 1920-1931, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-971502

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS: We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 µg, 100 µg, or 250 µg. There were 15 participants in each dose group. RESULTS: After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-µg group, 109,209 in the 100-µg group, and 213,526 in the 250-µg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-µg dose group reported one or more severe adverse events. CONCLUSIONS: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , RNA, Messenger/immunology , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/therapeutic use , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibody Formation , Betacoronavirus , COVID-19 , COVID-19 Vaccines , Female , Humans , Immunization, Secondary , Male , SARS-CoV-2 , T-Lymphocytes/immunology , Viral Vaccines/adverse effects , Young Adult
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