The clinical progress of mRNA vaccines and immunotherapies
AJ Barbier et al, Nature Biotechnology, May 9, 2022
Most clinical applications of mRNA to date have focused on vaccines for infectious disease and cancer for which low doses, low protein expression and local delivery can be effective because of the inherent immunostimulatory properties of some mRNA species and formulations. In addition, work on mRNA-encoded protein or cellular immunotherapies has also begun, for which minimal immune stimulation, high protein expression in target cells and tissues, and the need for repeated administration have led to additional manufacturing and formulation challenges for clinical translation. Building on this momentum, the past year has seen clinical progress with second-generation coronavirus disease 2019 (COVID-19) vaccines, Omicron-specific boosters and vaccines against seasonal influenza, Epstein–Barr virus, human immunodeficiency virus (HIV) and cancer.
COVID-19 and resilience of healthcare systems in ten countries
C Arsenault et al, Nature Medicine, March 14, 2022
We used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income? (Ghana, Lao People’s Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26–96% declines). Total outpatient visits declined by 9–40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods.
HIV variant causes concern
K O'Leary, Nature Medicine, February 14, 2022
Since human immunodeficiency virus (HIV) first appeared, it has diverged into various subtypes across the globe. These continue to evolve and vary in terms of their virulence (capacity to harm the host) and transmissibility; therefore, monitoring these features in circulating variants is important for public health. A new study noted that a small group of 17 people in the BEEHIVE study — an international surveillance project — were infected with a distinct subtype-B variant of HIV. They had exceptionally high viral loads at diagnosis, and most were in the Netherlands.
SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape
S Cele et al, Cell, January 13, 2022
We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral but evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.