Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3–4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4 + CD40L + T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT + patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

Background: Viral respiratory tract infections (VRI) are a major reason for hospitalization in children younger than 5 years. A case control study was conducted to investigate the potential role of breastfeeding in protecting children <1 year of age from VRI. Methods: Patients admitted for a respiratory tract infections routinely underwent a nasopharyngeal aspirate, which was tested with an RT-PCR for 14 respiratory viruses. Hospitalized infants positive for viruses were enrolled as cases; healthy controls were enrolled among patients admitted for ultrasound hip screening. The effect of breastfeeding on pertussis was investigated through multivariable analysis. Results: We enrolled a total of 496 patients: 238 cases and 258 healthy controls. Among cases, eighty-six patients (36.1%) had a rinovirus, 78 (32.8%) an RSV, 22 (9.2%) an adenovirus, and 37 (15.5%) a coinfections with multiple viruses. The number of households was significantly higher in cases (mean in cases 4.5; mean 3.7 in controls, p < 0.001) and the proportion of infants having siblings (79% in cases vs. 43% in controls, p < 0.001). Proportion of smoking mothers was higher in cases than in controls (21.4 vs. 10.1%, p = 0.001). Among cases 44.5% were exclusively breastfed at symptoms onset vs. 48.8% of healthy controls. According to the multivariable analysis, being exclusively breastfed at symptom onset was associated with a higher risk of viral respiratory infection (3.7; 95% CI 1.64–8.41), however a longer breastfeeding duration was protective (OR 0.98; 95% CI 0.97–0.99). Also having at least one sibling was associated to a higher risk (OR 3.6; 95% CI 2.14–5.92) as well as having a smoking mother (OR 2.6; 95% CI 1.33–4.89). Conclusions: Breastfeeding remains a mainstay of prevention for numerous diseases and its protective role increases with duration. However, being breastfed when mothers carry a respiratory infection may increase the risk of transmission, acting as a proxy for closer contacts. In future studies, potential confounding variables as pattern of contacts with other individuals, should be taken into account.