Pam2CSK4-adjuvanted SARS-CoV-2 RBD nanoparticle vaccine induces robust humoral and cellular immune responses.

As the global COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, vaccines remain an important tool for preventing the pandemic. The inactivated or subunit vaccines themselves generally exhibit low immunogenicity, which needs adjuvants to improve the immune response. We previously developed a receptor binding domain (RBD)-targeted and self-assembled nanoparticle to elicit a potent immune response in both mice and rhesus macaques. Herein, we further improved the RBD production in the eukaryote system by in situ Crispr/Cas9-engineered CHO cells. By comparing the immune effects of various Toll-like receptor-targeted adjuvants to enhance nanoparticle vaccine immunization, we found that Pam2CSK4, a TLR2/6 agonist, could mostly increase the titers of antigen-specific neutralizing antibodies and durability in humoral immunity. Remarkably, together with Pam2CSK4, the RBD-based nanoparticle vaccine induced a significant Th1-biased immune response and enhanced the differentiation of both memory T cells and follicular helper T cells. We further found that Pam2CSK4 upregulated migration genes and many genes involved in the activation and proliferation of leukocytes. Our data indicate that Pam2CSK4 targeting TLR2, which has been shown to be effective in tuberculosis vaccines, is the optimal adjuvant for the SARS-CoV-2 nanoparticle vaccine, paving the way for an immediate clinical trial.

COVID-19 Symptoms and Deaths among Healthcare Workers, United States.

We evaluated whether demographics and COVID-19 symptoms predicted COVID-19 deaths among healthcare workers (HCWs) in the United States by comparing COVID-19 deaths in HCWs with 3 control groups (HCW nondeaths, non-HCW deaths, and non-HCW nondeaths) using a case-control design. We obtained patient-level data of 33 variables reported during January 1, 2020-October 12, 2021, in all US states. We used logistic regression analysis while controlling for confounders. We found that persons who were >50 years of age, male, Black, or Asian experienced significantly more deaths than matched controls. In addition, HCWs who died had higher risks for the most severe clinical indicators. We also found that the most indicative symptoms were preexisting medical conditions, shortness of breath, fever, cough, and gastrointestinal symptoms. In summary, minority, male, and older HCWs had greater risk for COVID-19 death. Severe clinical indicators and specific symptoms may predict COVID-19-related deaths among HCWs.

A review on COVID-19 transmission, epidemiological features, prevention and vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths over past two years. Currently, many countries have still not been able to take the pandemic under control. In this review, we systematically summarized what we have done to mitigate the COVID-19 pandemic, from the perspectives of virus transmission, public health control measures, to the development and vaccination of COVID-19 vaccines. As a virus most likely coming from bats, the SARS-CoV-2 may transmit among people via airborne, faecal-oral, vertical or foodborne routes. Our meta-analysis suggested that the R0 of COVID-19 was 2.9 (95% CI: 2.7-3.1), and the estimates in Africa and Europe could be higher. The median Rt could decrease by 23-96% following the nonpharmacological interventions, including lockdown, isolation, social distance, and face mask, etc. Comprehensive intervention and lockdown were the most effective measures to control the pandemic. According to the pooled R0 in our meta-analysis, there should be at least 93.3% (95% CI: 89.9-96.2%) people being vaccinated around the world. Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the anti-epidemic goals and vaccination fairness.