Isolation and characterization of spike S2-specific monoclonal antibodies with reactivity to pan-coronaviruses

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),theseventh coronavirus known to jump from intermediate hosts to humans,has resulted in a worldwide pandemic and caused immense economicdamage(Tan et al.,2020;Zhu et al.,2020).It is believed that coronavirus spillover may occur again in the future.Human exposure to a bat coro-navirus has been serologically confimed in a rural area of China,indi-cating that the coronavirus spillover occurred,although the origin andfrequency of spillovers are unclear(Wang et al.,2018).

Identification of broad neutralizing antibodies against Omicron subvariants from COVID-19 convalescents and vaccine recipients

Dear Editor,Omicron(B.1.1.529)was designated a variant of concern(VOC)on November 26,2021(Callaway,2021),and its subvariants BA.1,BA.2,and BA.3 emerged and circulated almost simultaneously(Desingu et al.,2022).BA.2 was more efficient in transmission and quickly overtook BA.1 to become the variant most frequently detected worldwide(Yamasoba et al.,2022a).Compared to the prototype SARS-CoV-2 spike protein(S),the BA.1 and BA.2 spike proteins harbor more than 30 mutations,of which 21 are identical between the two subvariants,while the BA.3 spike differs from BA.1 and BA.2 by 3 mutations in the receptor binding domain(RBD)(Fig.1A).More recently,BA.4 and BA.5(hereafter BA.4/5)emerged,sharing the same spike sequence and containing four additional mutations,Del69–70,L452R,F486V,and R493Q,compared with BA.2.BA.4/5 were detected first in South Africa and evolved independently of BA.2;they have spread widely and replaced BA.2 as the predominant VOC(Gruell et al.,2022b;Tegally et al.,2022).In addition,BA.2.75,derived from the BA.2 subvariant,harbors nine additional mutations in the spike protein compared with BA.2(Fig.1A).BA.4/5 and BA.2.75 have led to the continuous emergence of novel Omicron subvariants,including BF.7 and BQ.1.These new subvariants may be driving waves of pandemics.

SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals

Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb)and B cell differentiation are tightly regulated by T follicular help (T_(FH)) cells. However, the longevity and functional role of T_(FH) cellsubsets in COVID-19 convalescents and vaccine recipients remain poorly defined. Here, we show that SARS-CoV-2 infection andinactivated vaccine elicited both spike-specific CXCR3^(+) T_(FH) cell and CXCR3^(-) T_(FH) cell responses, which showed distinct responsepatterns. Spike- specific CXCR3^(+) T_(FH) cells exhibit a dominant and more durable response than CXCR3^(-) T_(FH) cells that positivelycorrelated with antibody responses. A third booster dose preferentially expands the spike-specific CXCR3^(+) T_(FH) cell subset inducedby two doses of inactivated vaccine, contributing to antibody maturation and potency. Functionally, spike-specific CXCR3^(+) T_(FH) cellshave a greater ability to induce spike-specific antibody secreting cells (ASCs) differentiation compared to spike-specific CXCR3^(-) T_(FH)cells. In conclusion, the persistent and functional role of spike-specific CXCR3^(+) T_(FH) cells following SARS-CoV-2 infection andvaccination may play an important role in antibody maintenance and recall response, thereby conferring long-term protection. Thefindings from this study will inform the development of SARS-CoV-2 vaccines aiming to induce long-term protective immunememory.