Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Quantifying human-animal contact rates in Malaysian Borneo: Influence of agricultural landscapes on contact with potential zoonotic disease reservoirs.

Changing landscapes across the globe, but particularly in Southeast Asia, are pushing humans and animals closer together and may increase the likelihood of zoonotic spillover events. Malaysian Borneo is hypothesized to be at high risk of spillover events due to proximity between reservoir species and humans caused by recent deforestation in the region. However, the relationship between landscape and human-animal contact rates has yet to be quantified. An environmentally stratified cross-sectional survey was conducted in Sabah, Malaysia in 2015, collecting geolocated questionnaire data on potential risk factors for contact with animals for 10,100 individuals. 51% of individuals reported contact with poultry, 46% with NHPs, 30% with bats, and 2% with swine. Generalised linear mixed models identified occupational and demographic factors associated with increased contact with these species, which varied when comparing wildlife to domesticated animals. Reported contact rates with each animal group were integrated with remote sensing-derived environmental data within a Bayesian framework to identify regions with high probabilities of contact with animal reservoirs. We have identified high spatial heterogeneity of contact with animals and clear associations between agricultural practices and high animal rates. This approach will help inform public health campaigns in at-risk populations and can improve pathogen surveillance efforts on Malaysian Borneo. This method can additionally serve as a framework for researchers looking to identify targets for future pathogen detection in a chosen region of study.

An Antigenic Thrift-Based Approach to Influenza Vaccine Design.

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host's immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution - antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.