BCSnob wrote:

Here is a research study that combined two of my interests: science and sheep.

Immunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheep
BioRxiv Preprint 12Dec2022

In summary: sheep were immunized with the spike of the "original Wuhan SARS-CoV-2 sequence with an additional D614G mutation". This produced an immune response in these yearling ewes similar to what the vaccines induce in humans. The ewes with the highest antibody titers were bred and boosted prior to lambing. The milk these ewes produced was tested for antibodies against wuhan, beta, delta, and omicron; and these titers were compared to those for REGN-33 and REGN-87 (currently available antibody drugs). The sheep milk yielded neutralization against wuhan, beta, delta, and omicron which was broader in variant response than either of the antibody drugs. Immunized sheep milk could be used to generate large quantities of antibody treatments in place of human convalescent serum.

This is old technology; we boost our ewes before lambing to ensure they pass along important antibodies through their milk to their lambs.

Quote:

Introduction
Some early commentators bullishly predicted the end of the COVID-19 pandemic 1–4, with the build-up of vaccine and natural immunity eventually curtailing SARS-CoV-2 transmission. However, the pandemic is now entering its fourth year despite a vast burden of prior infection, over 13 billion vaccination doses globally 5 and high prevalence of anti-SARS-CoV-2 antibodies 6,7. Consistent with early-pandemic warnings 8–13, the pace of immune evasion has proven rapid 14,15, and transmission has continued robustly in the post-vaccine era 16. Warnings about insufficient vaccine acceptance 17, rapid waning of vaccine and post-infection immune protection 18,19, and antibody evasion 8–10,20 have all materialized at this point 21–23, leading to the high levels of SARS-CoV-2 transmission.

The ability of SARS-CoV-2 to evade immunity through mutations that degrade antibody binding has been a major driver of high and variable viral transmission. Indeed, the post-omicron era of the pandemic has been marked by successive waves driven by immune-evading subvariants, including BA.1, BA.5, XBB, and XBB.1.5 14,22,24–26. These immune-evading strains acquire an evolutionary advantage in the context of widespread immunity through mutations that degrade the binding of antibodies induced by infection with prior strains or by vaccines (“antigenic drift”)27. As neutralizing antibodies mediate sterilizing immunity to SARS-CoV-2–that is, they block infection upon exposure—evasion of these antibodies promotes reinfection 28. This advantage has allowed these immune-evading strains to achieve dominance, drive spikes in transmission, and replace (succeed) pre-existing strains 20. Between December 2021 (initial dissemination of the original BA.1 omicron variant) and December 2022, several strain succession events were documented resulting in an approximately 35-fold loss in neutralizing titer 29.

Understanding the potential of emerging strains to drive waves of infection, persist in circulation, and co-circulate with pre-existing strains is vital for understanding and reacting to this volatile phase of the pandemic. Immune evasion has implications for short-term and long-term transmission levels 30, possible changes in disease severity (manuscript in preparation), and the efficacy of vaccines and therapeutics, especially monoclonal antibodies 22,31. Anticipating the behavior of viral variants has tremendous practical significance for designing nonpharmaceutical and biomedical interventions.

In this study, we use an epidemiological modeling framework to build a quantitative understanding of the role of immune evasion in inter-strain competition and selection dynamics under endemic conditions. To this end, we developed a two-strain Susceptible-Infectious-Recovered-Susceptible (SIRS) model accounting for variable cross-immunity between a pre-existing and an invading strain. This paper explores viral evolutionary strategies by simulating a few relevant immunological scenarios: antigenic drift, which we surmise may be symmetric or unilateral, and induction of less durable immunity.

Antigenic drift results in reduced cross-immunity (immunity induced by one strain against another) compared to homologous immunity (immunity induced by a strain against itself) 32. If the impact of antigenic drift is symmetric, the invading strain’s cross immunity against the original strain will equal the original strain’s cross immunity against the invading strain. The plausibility of this scenario is supported by the tolerance of SARS-CoV-2’s spike for a wide variety of mutations 8,33,34. However, omicron BA.1 appeared to benefit from essentially unilateral antigenic drift: while BA.1 strongly evaded pre-existing immunity to delta, the delta was impeded by immunity induced by BA.1 35. The final scenario regards the possibility of viral strains with reduced durability of immunological protection from reinfection. Possibly exemplifying this scenario is omicron, which appears to exert weaker protection against homologous reinfection than delta (prior omicron reduces risk of omicron reinfection by 59.3%; prior delta infection reduces risk of delta reinfection by 92.3%, 36.)

Determining the immunological properties likely to be selected for is crucial for predicting the trajectory of SARS-CoV-2 under widespread transmission. Although the rapid pace of SARS-CoV-2 evolution and the simultaneous emergence of immune-evading multiple variants paints a complex picture 37,38, this simplified analysis provides a basis for understanding the inter-strain competition and selection that underpin these dynamics. Identifying the characteristics of strains likely to be successful and drive significant waves of transmission is crucial to support early-warning systems. Co-circulation of viral serotypes – that is, viral strains sufficiently antigenically distinct to coexist 39 – is an emergent threat that requires greater understanding and may lead to dramatically worse outcomes in the long-term trajectory of the pandemic.

Quote:

Abstract
SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific
CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.