Receptor binding domain-IgG levels correlate with protection in residents facing SARS-CoV-2 B.1.1.7 outbreaks.

Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS-CoV-2 and severe COVID-19, and its association with post-vaccine humoral response. 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-qPCR). SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-qPCR-positive residents and serum neutralizing antibodies in vaccinated residents from one NH. The incidence of positive RT-qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non-vaccinated residents (21/48; 43.7%; p < .01). COVID-19-induced deaths were observed in 5 of the 48 non-vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non-vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD-IgG (n = 325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1050 AU/ml. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe COVID-19. Two BNT162b2 doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. Post-vaccine RBD-IgG levels correlate with BNT162b2 protection against SARS-CoV-2 B.1.1.7.

Blain H ，Tuaillon E ，Gamon L ，Pisoni A ，Miot S ，Delpui V ，Si-Mohamed N ，Niel C ，Rolland Y ，Montes B ，Groc S ，Rafasse S ，Dupuy AM ，Gros N ，Muriaux D ，Picot MC ，Bousquet J ... -  《-》

Strong Decay of SARS-CoV-2 Spike Antibodies after 2 BNT162b2 Vaccine Doses and High Antibody Response to a Third Dose in Nursing Home Residents.

To measure the antibody decay after 2 BNT162b2 doses and the antibody response after a third vaccine dose administered 6 months after the second one in nursing home residents with and without prior COVID-19. Cohort study. Four hundred-eighteen residents from 18 nursing homes. Blood receptor-binding domain (RBD)-IgG (IgG II Quant assay, Abbott Diagnostics; upper limit: 5680 BAU) and nucleocapsid-IgG (Abbott Alinity) were measured 21‒28 days after the second BNT162b2 dose, as well as 1‒3 days before and 21‒28 days after the third vaccine dose. RBD-IgG levels of ≥592 BAU/mL were considered as high antibody response. Residents with prior positive quantitative reverse transcription polymerase chain reaction on a nasopharyngeal swab or with N-IgG levels above 0.8 S/CO were considered as prior COVID-19 residents. In prior COVID-19 residents (n = 122), RBD-IgG median levels decreased by 82% in 167 days on average. In the same period, the number of residents with a high antibody response decreased from 88.5% to 54.9% (P < .0001) and increased to 97.5% after the third vaccine dose (P = .02 vs the first measure). In residents without prior COVID-19 (n = 296), RBD-IgG median levels decreased by 89% in 171 days on average. The number of residents with a high antibody response decreased from 29.4% to 1.7% (P < .0001) and increased to 88.4% after the third vaccine dose (P < .0001 vs the first measure). The strong and rapid decay of RBD-IgG levels after the second BNT162b2 dose in all residents and the high antibody response after the third dose validate the recommendation of a third vaccine dose in residents less than 6 months after the second dose, prioritizing residents without prior COVID-19. The slope of RBD-IgG decay after the third BNT162b2 dose and the protection level against SARS-CoV-2 B.1.1.529 (omicron) and other variants of concern provided by the high post-boost vaccination RBD-IgG response require further investigation in residents.

Blain H ，Tuaillon E ，Gamon L ，Pisoni A ，Miot S ，Picot MC ... -  《-》

Are SARS-CoV-2 Antibodies Detectable in Human Milk After Vaccination Against COVID-19?

Human milk (HM) permits transfer of immunity against infections to infants via bioactive factors. The role of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HM is poorly understood [1, 2]. This study evaluated SARS-CoV-2 antibodies in the HM of vaccinated healthcare workers (HCW). This prospective study of 122 HCWs was performed from February to April 2021 at the Hospital Universitario Nuestra Señora de Candelaria. Immunoglobulin G (IgG) against nucleocapsid protein and IgG, immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies against spike 1 protein receptor-binding domain against SARS-CoV-2 (anti-SARS-CoV-2 RBD-S1) were analyzed. Unvaccinated breastfeeding mothers without COVID-19 were the control group.The 98 vaccinated participants underwent serum and HM evaluation 14 days after receiving 2 doses of either BNT162b2 mRNA (94%) or mRNA-1273 (6%) coronavirus disease 2019 (COVID-19) vaccines. The mean SARS-CoV-2 RBD-S1 IgG serum concentration was 3379.64 binding antibody units (BAUs)/mL with neutralizing antibody titers >560.9 BAUs/mL. Serum SARS-CoV-2 antibodies in the 24 unvaccinated participants were negative. The HM from vaccinated participants had anti-SARS-CoV-2 RBD-S1 IgG with a mean of 12.19 BAUs/mL compared to 0.02 BAUs/mL (P < .001) in HM from unvaccinated participants. Anti-SARS-CoV-2 S1 IgA was noted in 89% of HM from vaccinated women; no anti-SARS-CoV-2 S1 IgM was detected.A positive correlation was reported between anti-SARS-CoV-2 RBD-S1 IgG in serum and HM (r = 0.36; P < .001). This association was stronger if breastfeeding had been <24 months (r = 0.67; P < .001) vs ≥24 months (r = 0.32; P = 0.19). In subgroup analysis, breastfeeding for >24 months and high serum anti-SARS-CoV-2 RBD-S1 IgG levels predicted high HM IgG levels. This was an independent association in both linear and multiple regression models. Compared with breastfeeding <24 months, lactation >24 months was associated with increased HM anti-SARS-CoV-2 RBD-S1 levels. This study in breastfeeding HCWs showed that the HM antibody levels were higher in women who had been breastfeeding for >24 months prior to receiving 2 doses of COVID-19 vaccine compared to participants who had been breastfeeding <24 months. Limitations include lack of in vitro plaque reduction neutralization tests which is the gold standard for evaluating SARS-CoV-2 antibody deactivation effectiveness. The study was conducted at a single site and did not assess infant serology or clinical outcome.According to the authors, breastfeeding by vaccinated women during a pandemic when young children are ineligible for vaccination may be encouraged. These results support findings from other studies of vaccines, such as influenza, in which the HM of vaccinated women may confer protection to their infants [3]. The benefits of maternal immunization, including the duration of protection afforded by HM from maternal recipients of mRNA COVID-19 vaccines, are research areas deserving of additional exploration. Additionally, further understanding of the association of the duration of receipt of HM from vaccinated women on infant immune responses would be beneficial in understanding the potential for passive protection through nutrition.

Scaggs Huang F 《-》

Persistence and Protective Potential of SARS-CoV-2 Antibody Levels After COVID-19 Vaccination in a West Virginia Nursing Home Cohort.

Smoot K ，Yang J ，Tacker DH ，Welch S ，Khodaverdi M ，Kimble W ，Wen S ，Amjad A ，Marsh C ，Perrotta PL ，Hodder S ... -  《JAMA Network Open》

Poor Antibody Response to BioNTech/Pfizer Coronavirus Disease 2019 Vaccination in Severe Acute Respiratory Syndrome Coronavirus 2-Naive Residents of Nursing Homes.

Residents of nursing homes (NHs) are at high risk of coronavirus disease 2019 (COVID-19)-related disease and death and may respond poorly to vaccination because of old age and frequent comorbid conditions. Seventy-eight residents and 106 staff members, naive to infection or previously infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2), were recruited in NHs in Belgium before immunization with 2 doses of 30 µg BNT162b2 messenger RNA (mRNA) vaccine at days 0 and 21. Binding antibodies (Abs) to SARS-CoV-2 receptor-binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Abs against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. SARS-CoV-2-naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of immunoglobulin (Ig) G to all spike domains, lower avidity of RBD IgG, and lower levels of Abs neutralizing the vaccine strain. No naive residents had detectable neutralizing Abs to the B.1.351 variant. In contrast, SARS-CoV-2-infected residents had high responses to mRNA vaccination, with Ab levels comparable to those in infected staff. Cluster analysis revealed that poor vaccine responders included not only naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. The poor Ab responses to mRNA vaccination observed in infection-naive NH residents and in some naive staff members suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

Pannus P ，Neven KY ，De Craeye S ，Heyndrickx L ，Vande Kerckhove S ，Georges D ，Michiels J ，Francotte A ，Van Den Bulcke M ，Zrein M ，Van Gucht S ，Schmickler MN ，Verbrugghe M ，Matagne A ，Thomas I ，Dierick K ，Weiner JA ，Ackerman ME ，Goriely S ，Goossens ME ，Ariën KK ，Desombere I ，Marchant A ... -  《-》