Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination

PEDIATRICS ◽  
2022 ◽  
Author(s):  
Stephanie E. Perez ◽  
Luis Diego Luna Centeno ◽  
Wesley A. Cheng ◽  
Carolyn Jennifer Marentes Ruiz ◽  
Yesun Lee ◽  
...  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies have been detected in human milk up to 6 weeks post–coronavirus disease 2019 (COVID-19) vaccination. We evaluated SARS-CoV-2-specific antibodies, neutralization activity, effect of pasteurization, and persistence through 6 months after vaccination. METHODS: This prospective longitudinal study enrolled 30 pregnant or lactating women. SARS-CoV-2 antibodies and neutralization capacity were analyzed using an enzyme-linked immunosorbent assay compared at prevaccination and 1, 3, and 6 months postvaccination, and through Holder pasteurization. RESULTS: Human milk SARS-CoV-2-specific IgG levels peaked at 1 month postvaccination and persisted above prevaccination levels for at least 6 months (P = .005). SARS-CoV-2-specific IgA was detected at 1 and 3 months (both P < .001) but waned by 6 months compared with baseline (P = .07). Milk SARS-CoV-2-specific IgG and IgA correlated with serum IgG at the same time point (R2 = 0.37, P < .001 and R2 = 0.19, P < .001). Neutralization activity was seen in 83.3%, 70.4%, and 25.0% of milk samples at 1, 3, and 6 months postvaccination. Neutralization most strongly correlated with SARS-CoV-2-specific IgG (R2 = 0.57, P < .001). Pre- and postpasteurization samples showed similar IgG (0.84 vs 1.07, P = .36) and neutralizing activity (57.7% vs 58.7% inhibition, P = .27), but lower IgM and IgA levels postpasteurization (0.09 vs 0.06, P = .004 and 0.21 vs 0.18, P = .043). CONCLUSIONS: The data suggest that human milk SARS-CoV-2-specific antibodies may be available to milk-fed infants for up to 6 months. In addition, donor milk from vaccinated mothers retain IgG and neutralizing activity.

2021 ◽  
pp. 089033442110271
Author(s):  
Hannah G. Juncker ◽  
Sien J. Mulleners ◽  
Marit J. van Gils ◽  
Christianne J. M. de Groot ◽  
Dasja Pajkrt ◽  
...  

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being administered around the world; however, lactating women were excluded from SARS-CoV-2 vaccine trials. Therefore, knowledge about the effect of vaccination in this specific group is limited. This information is essential to empower lactating women to make a well-informed decision on their choice for vaccination. After natural infection, SARS-CoV-2 specific antibodies are present in human milk, which might offer protection for her newborn. The dynamics of these antibodies in human milk following vaccination remain to be elucidated. Research Aim To determine the effect of vaccination with BNT162b2 on the levels of SARS-CoV-2 specific IgA in human milk. Methods In this prospective longitudinal study, we included lactating women who received the BNT162b2 vaccine. Human milk samples were collected prior to vaccination and 3, 5, 7, 9, 11, 13, and 15 days after both vaccine doses. Samples were analyzed using enzyme-linked immunosorbent assay against the spike protein of SARS-CoV-2. Results In total, 366 human milk samples from 26 lactating women were analyzed. A biphasic response was observed, with SARS-CoV-2 specific immunoglobulin A (IgA) starting to increase between day 5 and 7 after the first dose of the vaccine. After the second dose, an accelerated IgA antibody response was observed. Conclusion After vaccination with the mRNA-based BNT162b2 vaccine, a SARS-CoV-2 specific antibody response was observed in human milk. The presence of SARS-CoV-2 specific IgA after vaccination is important as antibodies are transferred via human milk, and thereby might provide protection to infants against COVID-19.


2021 ◽  
Author(s):  
Nasamon Wanlapakorn ◽  
Nungruthai Suntronwong ◽  
Harit Phowatthanasathian ◽  
Ritthideach Yorsang ◽  
Thanunrat Thongmee ◽  
...  

Abstract Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous prime/booster-inactivated COVID-19 vaccine (CoronaVac) and adenoviral-vectored vaccine (AZD1222) were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 80) and AZD1222 (N = 80) regimen. All sera samples were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA). The neutralizing activity in a subset of serum samples was tested against the original Wuhan strain and variants of concern, B.1.1.7, B.1.617.2 and B.1.351, using an enzyme-linked immunosorbent assay (ELISA)-based surrogate virus neutralization test (sVNT). The heterologous CoronaVac/AZD1222 vaccine induced higher levels of spike RBD-specific IgG than that of two-dose homologous CoronaVac or AZD1222 vaccines (p < 0.001). Sera samples of the CoronaVac/AZD1222 vaccine recipients elicited higher neutralizing antibody activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. Nevertheless, there were no difference in neutralizing activity against the original Wuhan and B.1.1.7 strain among heterologous CoronaVac/AZD1222 and homologous AZD1222 vaccine recipients.


1988 ◽  
Vol 101 (3) ◽  
pp. 591-598 ◽  
Author(s):  
H. I. J. Thomas ◽  
P. Morgan-Capner

SUMMARYAn antiglobulin enzyme-linked immunosorbent assay for rubella-specific IgG1and IgG3was adapted to measure antibody avidity by incorporating a mild protein denaturant, diethylamine (DEA), into the serum diluent. Sera were tested at varying dilutions, both with and without DEA, if they contained sufficient specific IgG1or IgG3. The optical density (OD) was measured and curves were plotted. The highest OD (V) was noted and halved (V/2). The distance between the OD curves at V/2 was measured as the DEA shift value.Sera were examined from people whose sera contained rubella-specific antibodies as a consequence of infection or vaccination in the distant past (24 sera), recent primary rubella (66 sera), symptomatic reinfection (11 sera) or asymptomatic reinfection (64 sera). For specific IgG1the DEA shift value was <O·6 for cases of rubella in the distant past, compared with >0·8 for the first month after primary infection. The maximum DEA shift value for the sera from cases of reinfection was 0·65.No serum from cases of rubella in the distant past contained sufficient specific IgG3to estimate avidity. The sera collected within 1 month of onset of primary rubella gave DEA shift values >O·7 compared with sera from reinfections, which gave DEA shift values <O·6, except for two sera from a case of symptomatic reinfection.Thus the assessment of specific IgG subclass avidity is of value in differentiating serologically primary rubella from reinfection.


2021 ◽  
Author(s):  
Findra Setianingrum ◽  
Anna Rozaliyani ◽  
Robiatul Adawiyah ◽  
Ridhawati Syam ◽  
Mulyati Tugiran ◽  
...  

AbstractObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary tuberculosis (TB). CPA may also be misdiagnosed as bacteriologically-negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia; a country with a high incidence of TB.MethodsIn this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (>3 months), characteristic radiological features and positive Aspergillus serology, and categorized as proven, probable and possible.ResultsOf the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence of proven and probable CPA at baseline was 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (2 with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA.ConclusionCPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.Key messagesWhat is the key question?Do what extent is chronic pulmonary aspergillosis (CPA) both a) mistaken for TB and b) co-exists with TB during the course of 6 months therapyWhat is the bottom line?Features consistent with CPA were present in 6% of patients when starting TB therapy and 8% at the end of therapy, with some resolving and some developing CPA de novo during TB therapy. At the end of B therapy symptoms, cavitations with Aspergillus-specific IgG detectable were the key features of CPA.Why read on?Co-existence of TB and CPA is present in a substantial minority of patients starting and ending TB therapy, and needs addressing in terms of diagnosis, dual therapy and follow up.


mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Guillaume Beaudoin-Bussières ◽  
Annemarie Laumaea ◽  
Sai Priya Anand ◽  
Jérémie Prévost ◽  
Romain Gasser ◽  
...  

ABSTRACT In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. IMPORTANCE While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.


2019 ◽  
Vol 20 (13) ◽  
pp. 3158 ◽  
Author(s):  
Xinle Cui ◽  
Zhouhong Cao ◽  
Shuishu Wang ◽  
Michael Flora ◽  
Stuart P. Adler ◽  
...  

Congenital human cytomegalovirus (HCMV) infection and HCMV infection of immunosuppressed patients cause significant morbidity and mortality, and vaccine development against HCMV is a major public health priority. HCMV envelope glycoproteins gB, gH, and gL, which constitute the core fusion machinery, play critical roles in HCMV fusion and entry into host cells. HCMV gB and gH/gL have been reported to elicit potent neutralizing antibodies. Recently, the gB/gH/gL complex was identified in the envelope of HCMV virions, and 16–50% of the total gH/gL bound to gB, forming the gB/gH/gL complex. These findings make the gB/gH/gL a unique HCMV vaccine candidate. We previously reported the production of HCMV trimeric gB and gH/gL heterodimers, and immunization with a combination of trimeric gB and gH/gL heterodimers elicited strong synergistic HCMV-neutralizing activity. To further improve the immunogenicity of gH/gL, we produced trimeric gH/gL. Rabbits immunized with HCMV trimeric gH/gL induced up to 38-fold higher serum titers of gH/gL-specific IgG relative to HCMV monomeric gH/gL, and elicited ~10-fold higher titers of complement-dependent and complement-independent HCMV-neutralizing activity for both epithelial cells and fibroblasts. HCMV trimeric gH/gL in combination with HCMV trimeric gB would be a novel promising HCMV vaccine candidate that could induce highly potent neutralizing activities.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216464
Author(s):  
Findra Setianingrum ◽  
Anna Rozaliyani ◽  
Robiatul Adawiyah ◽  
Ridhawati Syam ◽  
Mulyati Tugiran ◽  
...  

ObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB.MethodsIn this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0–8 weeks) and at the end (5–6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible.ResultsOf the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA.ConclusionCPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.


Author(s):  
Enqing Tan ◽  
Erica Frew ◽  
Jeff Cooper ◽  
John Humphrey ◽  
Matthew Holden ◽  
...  

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants and antibodies that are escaped by these variants have important implications in the development of therapeutic and diagnostic solutions as well as in improving understanding of the humoral response to SARS-CoV-2 infection. We characterized seven anti-RBD monoclonal antibodies for their binding activity, pairing capability and neutralization activity to SARS-CoV-2 and three variant RBDs (UK, SA and BR P.1) via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the SA and BR P.1 RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. Further, we demonstrated that the lateral flow immunoassay can be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. From these studies, the potential contributions of the mutations (N501Y, E484K and K417N/T) contained in these variants&rsquo; RBDs on antibody pairing capability, neutralization activity and therapeutic antibody targeting strategy are discussed.


2021 ◽  
pp. 089033442110213
Author(s):  
Anna Gustafsson ◽  
Ewa Johansson ◽  
Ewa Henckel ◽  
Stefan Lange ◽  
Kajsa Bohlin

Background Preterm infants are more susceptible to inflammatory complications than term infants. Human milk contains numerous bioactive components protecting the newborn infant. Antisecretory factor, a protein regulating secretory and inflammatory processes by complex binding with complement factors, is present in human milk. Research Aims To describe antisecretory factor (1) in mother’s own milk in term and preterm infants; and (2) in donor milk before and after Holder pasteurization. Methods The study was prospective, longitudinal, explorative, and descriptive. Antisecretory factor-compleasome was determined using sandwich enzyme-linked immunosorbent assay in longitudinal human milk samples over 12 weeks from mothers ( N = 87) of term ( n = 41) and of preterm ( n = 46) infants and 20 anonymized donor human milk samples before and after Holder pasteurization. Results Antisecretory factor-compleasome was overall higher in colostrum versus mature milk ( p < .001) and no difference was found in term or preterm colostrum ( p = .82). In mature milk, compleasome was higher and more variable in the preterm group ( p = .01). After Holder pasteurization, compleasome levels increased ( p < .001). Conclusion Antisecretory factor followed the pattern of other immunological factors with high levels in colostrum. After preterm birth, levels of antisecretory factor were higher and more variable in mature milk. Holder pasteurization did not degrade antisecretory factor, indicating preserved anti-inflammatory properties in donor human milk.


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