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1.
Nat Commun ; 12(1): 6222, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493103

ABSTRACT

The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity.


Subject(s)
Breast Feeding , COVID-19 Vaccines/genetics , RNA, Messenger/blood , Adult , Animals , Antibody Formation/genetics , Antibody Formation/physiology , Female , Humans , Milk/chemistry , RNA, Messenger/analysis , Vaccines, Synthetic/therapeutic use
2.
Nat Commun ; 12(1): 6250, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1493099

ABSTRACT

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as 'non-responders' not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , SARS-CoV-2/pathogenicity , Adult , Aged , Antibody Formation/physiology , Bayes Theorem , Female , Humans , Immunoglobulin G/metabolism , Male , Middle Aged , SARS-CoV-2/immunology
3.
mBio ; 12(5): e0190821, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1430166

ABSTRACT

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed in record time and show excellent efficacy and effectiveness against coronavirus disease 2019 (COVID-19). However, currently approved vaccines cannot meet the global demand. In addition, none of the currently used vaccines is administered intranasally to potentially induce mucosal immunity. Here, we tested the safety and immunogenicity of a second-generation SARS-CoV-2 vaccine that includes a stabilized spike antigen and can be administered intranasally. The vaccine is based on a live Newcastle disease virus vector expressing a SARS-CoV-2 spike protein stabilized in a prefusion conformation with six beneficial proline substitutions (AVX/COVID-12-HEXAPRO; Patria). Immunogenicity testing in the pig model showed that both intranasal and intramuscular application of the vaccine as well as a combination of the two induced strong serum neutralizing antibody responses. Furthermore, substantial reactivity to B.1.1.7, B.1.351, and P.1 spike variants was detected. Finally, no adverse reactions were found in the experimental animals at any dose level or delivery route. These results indicate that the experimental vaccine AVX/COVID-12-HEXAPRO (Patria) is safe and highly immunogenic in the pig model. IMPORTANCE Several highly efficacious vaccines for SARS-CoV-2 have been developed and are used in the population. However, the current production capacity cannot meet the global demand. Therefore, additional vaccines-especially ones that can be produced locally and at low cost-are urgently needed. This work describes preclinical testing of a SARS-CoV-2 vaccine candidate which meets these criteria.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Newcastle disease virus/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibody Formation/physiology , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Swine
4.
Blood Cancer J ; 11(9): 151, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1408475

ABSTRACT

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.


Subject(s)
COVID-19/immunology , Hematologic Neoplasms/immunology , Immunity, Humoral/drug effects , Rituximab/pharmacology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/drug effects , Antibodies, Viral/metabolism , Antibody Formation/drug effects , Antibody Formation/physiology , Antibody Specificity/drug effects , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Female , Follow-Up Studies , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/epidemiology , Hospitalization , Humans , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Rituximab/therapeutic use
6.
Clin Infect Dis ; 71(16): 2027-2034, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153138

ABSTRACT

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.


Subject(s)
COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Adult , Aged , Antibodies, Viral/metabolism , Antibody Formation/physiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Male , Middle Aged , Pandemics , Serologic Tests
7.
Nat Commun ; 12(1): 1403, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1117351

ABSTRACT

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.


Subject(s)
COVID-19 Vaccines/therapeutic use , SARS-CoV-2/pathogenicity , Animals , Antibodies, Neutralizing/immunology , Antibody Formation/physiology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Macaca , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , Viral Vaccines/therapeutic use
8.
Diabetes Metab Syndr ; 15(1): 193-196, 2021.
Article in English | MEDLINE | ID: covidwho-987531

ABSTRACT

BACKGROUND AND AIMS: Patients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM). METHODS: Records of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis. RESULTS: Thirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14-17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019). CONCLUSIONS: COVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.


Subject(s)
Antibodies, Viral/blood , Antibody Formation/physiology , COVID-19 Testing/trends , COVID-19/blood , Diabetes Mellitus, Type 2/blood , SARS-CoV-2/metabolism , Adult , Aged , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/immunology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/immunology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Young Adult
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