Understanding vaccine-mediated protection against SARS-CoV-2 is critical to overcoming the global COVID-19 pandemic. We investigate mRNA vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three-time points: before vaccination, after the first, and after the second doses. Following complete vaccination, both naïve and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naïve individuals were lower than in previously infected individuals. After the first vaccine dose, 1/3 rd of previously infected individuals lacked neutralizing antibodies; this was improved to 1/5 th after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals.

Background The neural basis of action understanding is a hotly debated issue. The mirror neuron account holds that motor simulation in fronto-parietal circuits is critical to action understanding including speech comprehension, while others emphasize the ventral stream in the temporal lobe. Evidence from speech strongly supports the ventral stream account, but on the other hand, evidence from manual gesture comprehension (e.g., in limb apraxia) has led to contradictory findings. Aims Here we present a lesion analysis of sign language comprehension. Sign language is an excellent model for studying mirror system function in that it bridges the gap between the visual-manual system in which mirror neurons are best characterized and language systems which have represented a theoretical target of mirror neuron research. Methods & Procedures Twenty-one life long deaf signers with focal cortical lesions performed two tasks: one involving the comprehension of individual signs and the other involving comprehension of signed sentences (commands). Participants' lesions, as indicated on MRI or CT scans, were mapped onto a template brain to explore the relationship between lesion location and sign comprehension measures. Outcomes & Results Single sign comprehension was not significantly affected by left hemisphere damage. Sentence sign comprehension impairments were associated with left temporal-parietal damage. We found that damage to mirror system related regions in the left frontal lobe were not associated with deficits on either of these comprehension tasks. Conclusions We conclude that the mirror system is not critically involved in action understanding.

With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity.

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