Copy-editor: Rob Camp
Paper of the Day
Blanchard EL, Vanover D, Bawage SS, et al. Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents. Nat Biotechnol 2021, published 3 February. Full-text: https://doi.org/10.1038/s41587-021-00822-w
Cas13 treatment for influenza and SARS-CoV-2? In this study, Philip Santangelo, Chiara Zurla, Emmeline L. Blanchard and colleagues used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and SARS-CoV-2 infection in mice and hamsters, respectively. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms.
Letizia AG, Ge Y, Vangeti S, et al. SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study. medRxiv 2021, posted 29 January. Full-text: https://doi.org/10.1101/2021.01.26.21250535
High transmission rate in a US Marine camp despite a 2-week home quarantine plus another 2-week quarantine at the camp. Would you have placed a bet on a 48% transmission rate after another 6 weeks (1079 out of 2247 young recruits)? The authors caution that “the crowded living conditions, demanding regimen and requirement for personal contact during basic training despite the pandemic leads not only to an increased risk for respiratory epidemics, but also potentially to higher exposure levels. The close quarters and constant contact among recruits that are needed for team building allows a viral infection to rapidly proliferate within a unit. The physically and mentally demanding training environment may also suppress immunity. These conditions may contribute to the high infection rate we observed during the six-week study period. These factors are not typically present in the civilian community.”
The worst is yet to come, though. A total of 19 out of 189 (10.1%, 1.1 cases per person-year) initially seropositive participants had at least one positive SARS-CoV-2 PCR result during the six-week study period. In other words: in crowded living conditions, the re-infection rate with SARS-CoV-2 can be quite high. Bad news for ‘herd immunologists’.
Monod M, Blenkinsop A, Xi X, et al. Age groups that sustain resurging COVID-19 epidemics in the United States. Science. 2021 Feb 2:eabe8372. PubMed: https://pubmed.gov/33531384. Full-text: https://doi.org/10.1126/science.abe8372
As of October 2020, individuals aged 20-49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one, and at least 65 / 100 COVID-19 infections originate from individuals aged 20-49 in the US.
McCarthy KR, Rennick LJ, Nambulli S, et al. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 2021, published 3 January. Full-text: https://science.sciencemag.org/content/early/2021/02/02/science.abf6950
Coronaviruses acquire substitutions (variants) more slowly than other RNA viruses, due to a proofreading polymerase. In the spike glycoprotein, we find recurrent deletions overcome this slow substitution rate. In this adaptive evolution class, Paul Duprex, Kevin McCarthy and colleagues explain that deletion variants transmit efficiently, and are present in novel lineages, including those of current global concern. Deletions frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies.
Collier D, De Marco A, Ferreira I, et al. SARS-CoV-2 B.1.1.7 escape from mRNA vaccine-elicited neutralizing antibodies. medRxiv 2021, posted 2 February. Full-text: https://doi.org/10.1101/2021.01.19.21249840
Ravindra Gupta, Dami Collier and colleagues assess immune responses following vaccination with mRNA-based vaccine BNT162b2. They measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild type Spike protein or the 8 mutations found in the B117 Spike protein. The vaccine sera exhibited a broad range of neutralizing titers against the wild type pseudoviruses that were modestly reduced against B117. Introduction of the E484K mutation led to a more substantial loss of neutralizing activity by vaccine-elicited antibodies over that conferred by the B117mutations alone.
Voysey M, Costa Clemens SA, Madhi SA, et al. Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine. Lancet Preprints 2021, posted 1 February. Full-text: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268
Andrew Pollard, Sarah Gilbert, Merryn Voysey and colleagues present data from Phase III efficacy trials of ChAdOx1 nCoV-19 in the United Kingdom and Brazil, and Phase I/II clinical trials in the UK and South Africa. They report that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and that protection did not wane during this initial 3-month period. The authors conclude that vaccination programs aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be optimal for rollout of a pandemic vaccine when supplies are limited.
Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021, published 3 February. Full-text: https://doi.org/10.1016/S1473-3099(20)30987-7
Weidong Yin, Yuliang Zhao, Zhiwei Wu and colleagues report the results of Sinovac’s CoronaVac safety and immunogenicity data in adults aged 60 years or older (previous publications: Zhang Y 2020,
Gao 2020). Reminder: CoronaVac™ is an inactivated virus vaccine. On 12 January, the government of São Paulo, Brazil, announced the overall effectiveness of the Sinovac vaccine to be 50,38%. The data was obtained with tests carried out on 12.508 volunteers in the country, all health professionals. According to a report of The New York Times (7 January), Sinovac has sold more than 300 million doses, mostly to low- and middle-income countries, accounting for about half of the total production of Sinovac. See also COVID Reference Vaccines.
Gerberding JL, Haynes BF. Vaccine Innovations — Past and Future. N Engl J Med 2021; 384:393-396. Full-text: Full-text: https://doi.org/10.1056/NEJMp2029466
A 4-page overview by Julie Gerberding and Barton Haynes. The authors anticipate that the future holds great promise for vaccine-mediated control of global pathogens but providing affordable access to effective vaccines for everyone who could benefit from them remains an important challenge. Difficulties facing vaccinologists now include
- predicting the type and timing of the next pandemic;
- developing vaccines to combat rapidly changing pathogens such as HIV-1, influenza, and multidrug-resistant bacteria;
- and establishing rapid-response strategies to control emerging and reemerging infectious diseases.