ABSTRACT
Background: SARS-CoV-2 vaccines capable of inducing broad and cross-reactive humoral and T cell responses help to fight against emerging variants. In this study we compared the immunogenicity and efficacy of modified vaccinia Ankara (MVA) based SARS-CoV-2 vaccine expressing furin-cleavage site inactivated stabilized spike (SdFCS) and nucleocapsid (N) delivered via intramuscular (IM), buccal or sublingual (SL) routes in rhesus macaques (RMs). Methods: Three groups (n=5/group) of RMs were immunized with MVA/SdFCS-N vaccine on weeks 0 and 4, via IM, buccal, or SL route. An additional group (control) received non-recombinant MVA via IM. IM vaccinations were delivered using needle and SL and buccal vaccinations were delivered using a needle-free injection device. All RMs were challenged with B.1.617.2 strain (Delta) of SARS-CoV-2 at week 8 via intratracheal and intranasal routes simultaneously. Various humoral and cellular immune parameters were determined post vaccination and challenge. SARS-CoV-2 subgenomic RNA (sgRNA) was measured to monitor virus replication in the upper (nose) and lower (lung) respiratory tract. Results: IM vaccination induced strong RBD-specific IgG antibody in serum, nose, throat, lung, and rectum. The serum antibody showed strong live virus neutralizing activity against WA-1/2020 (median of 415) and B.1.617.2 strains (median of 317). Serum from IM vaccinated animals also demonstrated strong non-neutralizing effector functions such as ADCD, ADCP and ADNKA. In addition, IM vaccination induced strong CD4 and CD8 T cell response in the blood that was directed against both S and N. In contrast, the SL and buccal vaccination-induced antibody showed lower neutralization titer against WA-1/2020 (143 and 302, respectively), and showed 4.5-fold lower cross reactivity neutralization titer against B.1.617.2 compared to WA-1/2020. Following challenge with B.1.617.2, the IM group RMs showed superior protection with 3 of the 5 animals being negative in upper and lower respiratory airways at Day 2. In contrast, no significant protection was observed in the SL group. Vaccine induced neutralizing and non-neutralizing antibody effector functions showed direct association with protection. Conclusion: Our findings showed that IM vaccination with improved MVA-based SARS-CoV-2 vaccine elicits cross-reactive antibody and T cell responses and protect against heterologous SARS-CoV-2 Delta challenge in RMs. They also showed IM vaccinations are superior to oral vaccinations.
ABSTRACT
We report clinical profile of hundred and nine patients with SARS CoV-2 infection, and whole genome sequences (WGS) of seven virus isolates from the first reported cases in India, with various international travel histories. Comorbidities such as diabetes, hypertension, and cardiovascular disease were frequently associated with severity of the disease. WBC and neutrophil counts showed an increase, while lymphocyte counts decreased in patients with severe infection suggesting a possible neutrophil mediated organ damage, while immune activity may be diminished with decrease in lymphocytes leading to disease severity. Increase in SGOT, SGPT and blood urea suggests the functional deficiencies of liver, heart, and kidney in patients who succumbed to the disease when compared to the group of recovered patients. The WGS analysis showed that these isolates were classified into two clades: I/A3i, and A2a (four according to GISAID: O, L, GR, and GH). Further, WGS phylogeny and travel history together indicate possible transmission from Middle East and Europe. Three S protein variants: Wuhan reference, D614G, and Y28H were identified predicted to possess different binding affinities to host ACE2.
ABSTRACT
Background: Maternal antibodies are important for infant immunity, and understanding the maternal and umbilical cord antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will be important for neonatal management and maternal vaccination strategies. Methods: The dynamics of maternal/ umbilical cord antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were analyzed in 81 samples from 69 pregnant women studied between April 2020 and January 2021. Binding IgG, IgA and IgM antibodies to RBD were measured by enzyme-linked immunosorbent assay (ELISA) in both maternal and cord blood. Neutralization was assessed using codon-optimized full-length G614 Spike-pseudotyped virus (VRC7480.D614G). Results: Among the 69 pregnant women, 57 were either symptomatic or asymptomatic infection and 17 samples were taken during the time of delivery resulting in paired maternal/umbilical cord blood samples. Among the maternal samples tested, the RBD specific IgG were detected in 93%, IgA were detected in 67% and IgM were detected in 79%. The RBD-specific IgG was detected in 12 of 17 (70%) umbilical cord blood, but IgM and IgA were not detected in the cord blood samples. The IgG antibody concentration were significantly (P < 0.004) lower (7 fold) in the cord blood when compared to maternal blood. However, the cord blood IgG titers were positively correlated with maternal IgG titers (r = 0.59;P < 0.003). In line with that, the circulating T-follicular helper cells (p<0.0001) and signaling lymphocytic activation molecule family 1(SLAMF1) were lower (p<0.004) in cord relative to maternal blood. Among the samples tested, 71.4% had neutralization titers. Interestingly, the neutralization capacity of plasma from cord blood was negative when compared to maternal blood (mean titer of 20 vs 2128 respectively), suggesting that cord blood does not have capacity to neutralize the SARS-CoV-2 virus. Conclusion: In this cohort study, maternal IgG, IgA and IgM antibodies to RBD of SARS-CoV-2 were seen in maternal samples. However the cord blood IgG levels were significantly lower and did not show positive titers for IgA and IgM. Although both maternal and cord blood has RBD binding antibodies, there is no neutralization seen in any of the cord blood tested compared to respective maternal blood. Our findings demonstrate that maternally-derived SARS-CoV-2 specific antibodies lack neutralization potential to provide neonatal protection from COVID-19. (Figure Presented).