Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally. As SARS-CoV-2 has transmitted from person to person, variant viruses have emerged with elevated transmission rates and higher risk of infection for vaccinees. We present data showing that a recombinant prefusion-stabilized Spike (rS) protein based on the B.1.351 sequence (rS-B.1.351) was highly immunogenic in mice and produced neutralizing antibodies against SARS-CoV-2/WA1, B.1.1.7, and B.1.351. Mice vaccinated with our prototype vaccine NVX-CoV2373 (rS-WU1) or rS-B.1.351 alone, in combination, or as a heterologous prime boost, were protected when challenged with live SARS-CoV-2/B.1.1.7 or SARS-CoV-2/B.1.351. Virus titer was reduced to undetectable levels in the lungs post-challenge in all vaccinated mice, and Th1-skewed cellular responses were observed. A strong anamnestic response was demonstrated in baboons boosted with rS-B.1.351 approximately one year after immunization with NVX-CoV2373 (rS-WU1). An rS-B.1.351 vaccine alone or in combination with prototype rS-WU1 induced protective antibody- and cell-mediated responses that were protective against challenge with SARS-CoV-2 variant viruses.

Overweight predicts poorer exercise capacity in congenital heart disease patients.

BACKGROUND: Overweight (OW) and obesity (OB) are endemic in the United States and affect adolescents and adults with congenital heart disease (ACHD). Defining the burden of excess weight on the cardiovascular system in ACHD is the goal of this study. Limitation of exercise capacity due to overweight or obesity might be reversible with weight loss and improve quality of life for ACHD adults. METHODS: Exercise tests performed using a Bruce protocol and measurement of maximum oxygen consumption were retrospectively reviewed on 418 CHD patients. OW and OB were defined as the 85-95 or > 95 percentile respectively for age and gender or by adult criteria. Severity of CHD was assigned based on criteria published in standard guidelines. RESULTS: 63 patients had mild, 198 moderate, and 157 severe heart disease. Each ACHD group was 32 to 34% OW or OB. Measured exercise time (ET) of CHD patients with moderate or severe heart disease was less than that of controls in each weight categories. However, OB or OW people have shorter ET than their normal weight peers with CHD. Multiple regression using ET as the dependent variable finds that female sex, relative BMI, and VE/VCO2 at peak exercise are all associated with lesser ET with high significance. Peak heart rate is associated with greater ET, with borderline significance. Severity of heart disease is not independently associated with ET. CONCLUSIONS: OW and OB are strongly associated with reduced ET in persons with congenital heart disease. Losing weight may improve exercise capacity in ACHD.