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PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333769


Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID 50 ) >10 3 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17, IFN- gamma , or TNF- alpha . Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity. ONE-SENTENCE SUMMARY: SARS-CoV-2 vaccines are well-tolerated and highly immunogenic in infant rhesus macaques.

PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293057


Background: To reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. Methods: Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. Results: We report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. Conclusions: Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Topics in Antiviral Medicine ; 29(1):237-238, 2021.
Article in English | EMBASE | ID: covidwho-1250195


Background: SARS-CoV-2 vaccines have shown promising efficacy in human adult trials, but immunogenicity and efficacy studies in the pediatric population are lagging behind. Here we evaluated the immunogenicity of two prefusion stabilized Spike protein (S-2P) vaccine platforms in infant Rhesus Macaques (RM): an adjuvanted S-P2 subunit and mRNA vaccine. Methods: Infant RMs (2.5 months-old) were immunized intramuscularly at weeks (wks) 0 & 4 with 15 μg S-P2 adjuvanted with the toll-like receptor 7/8 agonist 3M-052 in stable emulsion (n=8), or 30 μg of S-P2 mRNA in lipid nanoparticles (mRNA-LNP, Moderna) (n=8). Blood was collected at wks 0, 4, 6, 8, & 14. Plasma (Spike[S]) and salivary (receptor binding domain [RBD]) IgG responses were measured by ELISA and epitope specificity by multiparameter bead array. Antibody function was assessed by an ACE2 blocking assay and neutralization by pseudovirus (PSVA) and whole virus neutralization assays, both with D614G. Flow cytometry was applied to measure S-specific memory B cells using fluorochrome-conjugated recombinant S, and S-specific IL-2, IL-17, TNF-α, or IFN-γ producing T cells after stimulation with overlapping peptides of full-length S. Results: No adverse effects were observed with either vaccine. Plasma S-specific IgG responses were induced by both vaccines at wk 4, increased after the second dose, and persisted through wk 14 (Fig 1A). All S regions were targeted by plasma IgG (Fig 1B), and RBD-specific IgG was also detected in saliva. Serum antibodies achieved >95% ACE2 blocking by wk 6 (1:10 dilution), remaining >90% at wk 14. Geometric mean ID50 titers of neutralizing antibodies in the PSVA exceeded 10[3] from wk 6 through wk 14 (Fig 1C) and strongly correlated with whole virion neutralization (p<0.0001). In the protein vaccine group, S-specific CD27+ memory B cells peaked at 3.1% (mean) of total memory B cells;and S-specific CD4+ T cell responses were dominated by IL-17 and IFN-γ Mean S-specific CD27+ B cells peaked at 0.9% total memory B cells in mRNA vaccinees and S-specific CD4+ T cells produced IL-2, IFN-γ, IL-17, or TNF-α. Conclusion: The S-2P-3M-052-SE and mRNA-LNP vaccines were well-tolerated and highly immunogenic in infant Rhesus Macaques, with persistent IgG binding and neutralization responses that are comparable to those reported for adult RMs and humans. Our results provide proof-of-concept that a pediatric SARS-CoV-2 vaccine could induce long term protection against SARS-CoV-2.