mRNA Vaccines (Univercells/Altamira Therapeutics)

Vaccination with COVID-19 mRNA vaccines generates robust antibody responses, but the impact of prior infection on the quality of these responses, particularly immunoglobulin G (IgG) subclass profiles remain unclear. A longitudinal study was conducted to compare humoral immune responses in SARS-CoV-2 infection-naïve and pre-immune (previously infected) individuals following a two-dose mRNA vaccine primary series and a booster dose. Anti-spike receptor-binding domain (RBD) IgG levels, neutralizing antibody titers against the vaccine-matched (Wuhan-Hu-1) virus and the Omicron BA.1 variant, and IgG1-IgG4 subclass distributions over time were measured. After two doses, pre-immune participants had higher anti-RBD IgG (2-fold, p < .001) and neutralization titers than naïve participants (GMT±SD; 6407 ± 4 vs 5706 ± 3.5). Notably, 89.7% of pre-immune versus 28.1% of naïve sera neutralized Omicron BA.1 (p < .0001). However, a third (booster) raised antibody levels in naïve participants to a statistically similar titer to pre-immune participants (p > .05). The booster vaccination also markedly enhanced the titers of cross-neutralizing antibodies against Omicron BA.1 in both vaccine groups. This increased the proportion of responders from 31.8% to 95.5% in naïve participants. Booster vaccinations induced significant IgG4 titers in naïve (p < .0001), but not in pre-immune participants (p > .05) compared to primary series of vaccination levels. Both vaccinated naïve participants and pre-immune vaccinated participants had a breakthrough infection within one year following the booster vaccination (36.4% vs 25%, p > .05 respectively). We report that the presence of IgG4 antibodies, specifically in naïve individuals, did not alter in vitro virus neutralizing response against ancestral WH-1 and Omicron BA.1 variant, with comparable breakthrough infection rates.

mRNA vaccine had emerged as a novel and promising modality in cancer immunotherapy. As anti-tumor mRNA vaccines entered clinical trials, continuous monitoring of mRNA levels becomes particularly important. In this paper, a new method of collaborative detection of tumor mRNA vaccine by double Cas12a system based on split crRNA was created. Specifically, the target was extended based on the RCA ring template to generate RCA products and completed the first round of signal amplification; At this time, there were a lot of secondary structures in RCA products. Subsequently, the double Cas12a system with split crRNA bound to adjacent sites, reduced secondary structure of the DNA strand, stabilized the linearization state, and identified multiple sites at the same time, so as to achieve the second round of collaborative signal amplification. When there was no target in the system, the RCA reaction cannot be triggered. In this method, the entire detection process was completed by one-pot method. The detection limit was as low as 0.2pM, and it showed a good linear relationship in the range of 0-100 pM, which provided a new method for the screening and pharmacokinetics study of tumor mRNA vaccines.