The Bigger Picture: Coronavirus in the Context of the History of the American Film Industry

In the early days of the coronavirus pandemic, many commentators on American life predicted that people "would never” be able to do a variety of social activities again, even post-pandemic. Among these activities was going to movie theaters. Because theaters were already competing for audiences with the growing number of streaming services, and so many viewers migrated to streaming once lockdowns began, some observers argued that movie theaters would not survive the pandemic. This chapter argues that theaters will in fact survive, for two reasons: the history of the American film industry, including theatrical distribution, is a history of adaptation to threats;and human sociability will ensure that people will still go out to movies even when they can watch them at home. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

PROTECTION AGAINST HETEROLOGOUS CHALLENGE 1 YEAR AFTER INFANT SARS-CoV-2 IMMUNIZATION

Background: Although mRNA SARS-CoV-2 vaccines have received emergencyuse- authorization for infants age 6 months and older, vaccine uptake is slow, stressing that questions of safety and durability of vaccine efficacy remain prominent. Method(s): Infant rhesus macaques (RMs) (n=8/group) at 2 months of age, comparable to human toddler age, were immunized intramuscularly at weeks 0 and 4 with 30mug stabilized prefusion SARS-CoV-2 S-2P spike (S) protein (Washington strain) encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or 15mug S protein mixed with 3M-052 in stable emulsion (Protein). At 1 year, vaccinated and age-matched unvaccinated RM (n=8) were challenged intranasally (106pfu) and intratracheally (2x106pfu) with B.1.617.2. Lung radiographs and pathology were blindly assessed, viral N gene RNA (vRNA) copies were measured by qPCR in pharyngeal swabs and lung, and neutralizing antibody and peripheral blood T cell responses were measured. Result(s): At 1 year, D614G-specific neutralizing antibody (nAb) titers were still detectable in the Protein (ID50=755;range: 359-1,949) and mRNA-LNP groups (ID50=73;range: 41-240). Both vaccines also induced cross-neutralizing antibodies to B.1.617.2. Peripheral blood CD4+ T cell responses to the ancestral spike protein at week 52 did not differ between the groups. However, median CD8+ T cell responses were higher (p=0.002, Mann Whitney) in the mRNA-LNP group (2.8%;range: 0.9%-7.1%) compared to the Protein group (0.8%;range: 0.1%-1.6%). Control RMs had significantly higher median vRNA copies/ml (1.4+/-2.7x108) in day 4 pharyngeal swabs compared to Protein (3.8+/-6.8x103) or mRNA-LNP (4.4+/-9.7x105) vaccinated RMs. Severe lung pathology was observed in 7 of 8 controls compared to 1 of 8 or 0 of 8 RMs in the mRNA-LNP or Protein group respectively. Protection against lung inflammation was associated with nAb titers (r=-0.592, p=0.003) (Figure 1). Conclusion(s): These results demonstrate that despite lower vaccine doses compared to adults, both protein and mRNA vaccines were safe, induced durable immune responses and provided comparable protective efficacy against infection with a heterologous SARS-CoV-2 variant in infants, implying that early life vaccination of human infants may lead to durable immunity. Neutralizing ID50 antibody titers are a correlate of protection in infant RMs challenged with SARS-CoV-2.

Sars-cov-2 vaccines induce durable neutralizing antibodies in infant rhesus macaques

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.