The new US security strategy released by the White House in September 2002, is a remarkable document which requires more analysis than that received in the main media, perhaps partially because of the massive attention given to the Beltway sniper(s). The new strategy would justify pre-emptive strikes for the first time against any countries which the current or future US leadership believe might pose a threat in the future such as China or resurgent Russia or any other country or a group of countries. This bold assertion is justified by the threat of even more miniature weapons of mass destruction coupled with the hatred of America. This important document and the accompanying commentary provide essential and thought provoking reading.

The national security strategy of the United States of America

http://www.cell.com/article/S0092867422005335/pdf

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections2,3. Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles4,5, and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. 

/pdf/imprinted-sars-cov-2-humoral-immunity-induces-convergent-2s5rkc2l.pdf

Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

http://www.cell.com/article/S0092867422011904/pdf

Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

Abstract Omicron variant strains encode large numbers of changes in the spike protein compared to historical SARS-CoV-2 isolates. Although in vitro studies have suggested that several monoclonal antibody therapies lose neutralizing activity against Omicron variants, the effects in vivo remain largely unknown. Here, we report on the protective efficacy against three SARS-CoV-2 Omicron lineage strains (BA.1, BA.1.1, and BA.2) of two monoclonal antibody therapeutics (S309 [Vir Biotechnology] monotherapy and AZD7442 [AstraZeneca] combination), which correspond to ones used to treat or prevent SARS-CoV-2 infections in humans. Despite losses in neutralization potency in cell culture, S309 or AZD7442 treatments reduced BA.1, BA.1.1, and BA.2 lung infection in susceptible mice that express human ACE2 (K18-hACE2) in prophylactic and therapeutic settings. Correlation analyses between in vitro neutralizing activity and reductions in viral burden in K18-hACE2 or human FcγR transgenic mice suggest that S309 and AZD7442 have different mechanisms of protection against Omicron variants, with S309 utilizing Fc effector function interactions and AZD7442 acting principally by direct neutralization. Our data in mice demonstrate the resilience of S309 and AZD7442 mAbs against emerging SARS-CoV-2 variant strains and provide insight into the relationship between loss of antibody neutralization potency and retained protection in vivo. 

/pdf/resilience-of-s309-and-azd7442-monoclonal-antibody-2mk4xpf0.pdf

Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants. 

/pdf/characterization-and-antiviral-susceptibility-of-sars-cov-2-16oxyz3t.pdf

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

: Operational readiness and sustainment training allow military forces to be prepared for various types of contingency operations and provide for the primary means of protection and defense of United States national security interests. Readiness and sustainment training have suffered do to increased OPTEMPO and PERSTEMPO due to the rigors of missions and everyday operations, and complications brought on by budget, environmental and infrastructure constraints. This paper advocates the utilization of advanced distributed learning and distance learning in readiness and sustainment training. Advanced technology provides for a more learner-centric approach to training and can accelerate skills proficiency and retention of critical skills. This paper also examines DoD, Army and Air Force training doctrine, traditional vs non- traditional training, human resource and work place factors, cost effectiveness and benefits, and provides recommendations for capitalizing on alternative delivery platforms. The 1 March 2002 Strategic Plan for Transforming DoD Training touts the necessity of the Services, joint community, and OSD to exploit advanced technology in Total Force training. The increased use of alternative delivery training platforms will enable Army and Air Force personnel to become more effective and efficient in their job performance.

/pdf/leveraging-advanced-technology-in-army-and-air-force-1slq0ojd26.pdf

Kathy Lindsey

Papers

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

Leveraging Advanced Technology in Army and Air Force Readiness and Sustainment Training