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      SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk after vaccination with the protein subunit vaccine Abdala

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          Abstract

          Background

          COVID-19 vaccines that trigger a strong secretory antibody response in breast milk may achieve effective passive protection of vulnerable newborns and breastfed infants of immunized mothers. The aim of this work was to investigate the presence of SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk, 5 and 9 weeks after vaccination with three doses of the protein subunit vaccine Abdala, compared to those found in breast milk from COVID-19-recovered women, collected at least 40 days after the infection.

          Methods

          SARS-CoV-2 spike RBD-specific IgA and IgG antibodies were semi-quantified by indirect ELISA, using a homemade standard generated by pooling twenty breast milk samples with high absorbance values according to preliminary data. The validity of the standard curves was proved following the European Medicines Agency Guideline. Two breast milk samples from two unvaccinated women who had not been infected with COVID-19 were included as negative controls. Potentially neutralizing antibodies was assessed by a SARS-CoV-2 surrogate virus neutralization test.

          Results

          High levels of anti-RBD IgA antibodies was detected in breast milk samples 9 weeks after vaccination and anti-RBD IgG antibodies rise from the fifth to the ninth week. In the post-COVID-19 time that was evaluated, the IgG-type response was notably higher compared to both post-vaccination periods. Neutralizing antibody titers were similar in breast milk from vaccinated and COVID-19 recovered women.

          Conclusions

          This is the first report about the immune response in breast milk after the administration of a COVID-19 protein subunit vaccine, which could provide analogous protection to that conferred by SARS-CoV-2 infection. This implies a potential passive immunity that breastfed infants receive from their mothers vaccinated with Abdala.

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          Most cited references31

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          A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction

          A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.
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            Is Open Access

            IgA dominates the early neutralizing antibody response to SARS-CoV-2

            Early specific antibody responses against SARS-CoV-2 include IgG, IgM, and IgA, but IgA may neutralize virus and control infection to a larger extent.
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              COVID-19 vaccine response in pregnant and lactating women: a cohort study

              Background Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking. Objectives To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy. Study Design 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups. Results Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. Conclusions COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.
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                Author and article information

                Journal
                Infectious Medicine
                The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.
                2772-431X
                2772-431X
                18 November 2022
                18 November 2022
                Affiliations
                [a ]Research & Development Department. Center for Genetic Engineering and Biotechnology. Circunvalante Norte, Olivos III, Sancti Spiritus, Cuba
                [b ]Neonatology Service, General Hospital “Camilo Cienfuegos”, 128 Bartolome Maso, Sancti Spiritus, Cuba
                [c ]Production Department. Center for Genetic Engineering and Biotechnology. Circunvalante Norte, Olivos III, Sancti Spiritus, Cuba
                Author notes
                [* ]Corresponding author, Tel. (±53) 5522 5640
                Article
                S2772-431X(22)00055-7
                10.1016/j.imj.2022.11.001
                9671870
                9cb7ffce-3995-4b74-ae93-0c024e0f5d22
                © 2022 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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