COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV-2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection.

OBJECTIVES: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. DESIGN: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). RESULTS: Ninety-eight patients completed primary vaccination prepregnancy (29.6%) and antenatally (63.3%), 24.2% of whom had antenatal COVID-19, while 7.1% were unvaccinated (28.6% had antenatal COVID-19). None had severe COVID-19. Prepregnancy vaccination resulted in vaccination-to-infection delay of 23.3 weeks, which extended to 45.2 weeks with a booster, compared to 16.9 weeks following antenatal vaccination (P < 0.001). Infections occurred at 26.2 weeks gestation in women vaccinated prepregnancy compared to 36.2 weeks gestation in those vaccinated during pregnancy (P < 0.007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio [HR] 14.6, P = 0.05) and after prepregnancy vaccination without a booster (HR 10.4, P = 0.002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. CONCLUSION: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.

Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic pathways, inhibition of the Akt pathway, downregulation of ERα.

Acid ceramidase is the key enzyme of the ceramide metabolic pathway, which plays a vital role in regulating ceramide - sphingosine-1-phosphate rheostat. Ceramide acts as a proapoptotic molecule, but its metabolite sphingosine-1-phosphate, in contrast, signals for cell proliferation, cell survival, and angiogenesis. Acid ceramidase is highly upregulated in breast tumors and treatment with an acid ceramidase inhibitor, ceranib-2, significantly induced apoptosis in human breast cancer cell lines. However, the mechanisms underlying the induction of apoptosis remain ambiguous to date. Hence, in the present study, we have explored ceranib-2-mediated apoptotic signaling pathways in human breast cancer cell lines. MCF-7 and MDA MB-231 cells were treated with IC50 doses of ceranib-2 and tamoxifen. Nuclear changes showed the apoptotic effect of ceranib-2 in both the cell lines. Loss in the mitochondrial membrane potential was observed only in ceranib-2-treated MCF-7 cells. Ceranib-2 activated intrinsic and extrinsic apoptotic pathways in MCF-7 cells, but only the extrinsic apoptotic pathway was activated in MDA MB-231 cells. Further, ceranib-2 induced apoptosis by activating SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase), p38 MAPK (mitogen-activated protein kinase) apoptotic pathways and by inhibiting the Akt (antiapoptotic) pathway in both the cell lines. Most importantly, ERα (estrogen receptor-α) expression was highly downregulated after ceranib-2 treatment and a docking study predicted the highest binding affinity of ceranib-2 than tamoxifen with ERα in MCF-7 cells. Hence, ceranib-2 may have potential as a chemotherapeutic drug of breast cancer.