A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies.

SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.

The specificity of sperm-mediated paternal effects in threespine sticklebacks.

Parental effects may help offspring respond to challenging environments, but whether parental exposure to different environmental challenges induces similar responses in offspring is largely unknown. We compared the offspring of threespine stickleback (Gasterosteus aculeatus) fathers who had been exposed to a potentially threatening stimulus (net), a native predator (sculpin), or who had been left unexposed (control). Relative to offspring of control fathers, offspring of sculpin-exposed fathers were more responsive (greater change in activity) to a simulated sculpin predator attack, while offspring of net-exposed fathers were less responsive (fewer antipredator behaviors) and showed altered stress responses compared to the control. To evaluate whether parental exposure primes offspring to respond to specific stimuli (e.g., offspring of net-exposed fathers respond most strongly to a net), we then exposed offspring of each paternal treatment to nets, native sculpin models, or non-native trout models. Paternal treatment did not influence offspring response to different stimuli; instead, offspring were generally more responsive to the native sculpin predator compared to nets or non-native trout predator, suggesting that sticklebacks have innate predator recognition of native predators. Collectively, these results underscore that, while parental exposure to non-ecologically relevant stressors elicits effects in intergenerational studies, these findings may not mirror those produced when parents encounter ecologically relevant stressors. Knowing that parental effects can be predator-specific furthers our understanding of the ways in which parental effects may evolve to be adaptive and suggests the potential for transgenerational plasticity to affect how animals respond to human induced environmental change, including non-native predators.

Sex-specific plasticity across generations I: Maternal and paternal effects on sons and daughters.

Intergenerational plasticity or parental effects-when parental environments alter the phenotype of future generations-can influence how organisms cope with environmental change. An intriguing, underexplored possibility is that sex-of both the parent and the offspring-plays an important role in driving the evolution of intergenerational plasticity in both adaptive and non-adaptive ways. Here, we evaluate the potential for sex-specific parental effects in a freshwater population of three-spined sticklebacks Gasterosteus aculeatus by independently and jointly manipulating maternal and paternal experiences and separately evaluating their phenotypic effects in sons versus daughters. We tested the adaptive hypothesis that daughters are more responsive to cues from their mother, whereas sons are more responsive to cues from their father. We exposed mothers, fathers or both parents to visual cues of predation risk and measured offspring antipredator traits and brain gene expression. Predator-exposed fathers produced sons that were more risk-prone, whereas predator-exposed mothers produced more anxious sons and daughters. Furthermore, maternal and paternal effects on offspring survival were non-additive: offspring with a predator-exposed father, but not two predator-exposed parents, had lower survival against live predators. There were also strong sex-specific effects on brain gene expression: exposing mothers versus fathers to predation risk activated different transcriptional profiles in their offspring, and sons and daughters strongly differed in the ways in which their brain gene expression profiles were influenced by parental experience. We found little evidence to support the hypothesis that offspring prioritize their same-sex parent's experience. Parental effects varied with both the sex of the parent and the offspring in complicated and non-additive ways. Failing to account for these sex-specific patterns (e.g. by pooling sons and daughters) would have underestimated the magnitude of parental effects. Altogether, these results draw attention to the potential for sex to influence patterns of intergenerational plasticity and raise new questions about the interface between intergenerational plasticity and sex-specific selective pressures, sexual conflict and sexual selection.