Comparison of three different COVID-19 vaccine platforms (CoronaVac, BTN162b2, and Ad5-nCoV) in individuals with and without prior COVID-19: Reactogenicity and neutralizing antibodies.

Neutralizing antibodies (NAbs) can be indicators of collective immunity, vaccine efficacy, and the longevity of the humoral response. This study aimed to compare reactogenicity and NAbs generated by three different COVID-19 vaccine platforms in individuals with and without prior COVID-19. 336 individuals vaccinated (112 with CoronaVac [inactivated virus], 112 with BNT162b2 [messenger RNA], and 112 with Ad5-nCoV [non-replicating viral vector]) were included. NAbs were quantified with the cPass SARS-CoV-2 kit. Individuals immunized with the Ad5-nCoV showed higher reactogenicity than those immunized with the other vaccines (p < 0.001). The BTN162b2 vaccine-induced NAbs with higher inhibition capacity than the other platforms in the first dose. In individuals without prior COVID-19, the Ad5-nCoV vaccine generated lower NAbs against SARS-CoV-2 than those induced by two doses of the BTN162b2 (Ad5-nCoV 72.10 [55.6-93.4] vs. BTN162b2 98.41 [98.16-98.56], p < 0.0001). One individual did not generate NAbs (0.89%) after a complete immunization with CoronaVac; in BTN162b2, all generated these antibodies, and in the Ad5-nCoV group, four individuals (3.57%) did not generate NAbs. Comorbidities, gender, age, and reactogenicity did not significantly influence the generation of NAbs (p > 0.05); however, a history of COVID-19 before vaccination was associated with antibodies with greater neutralizing capacity after the first dose (p < 0.01). In conclusion, the mRNA vaccine (BTN162b2) had a remarkable better ability to produce NAbs and lower reactogenicity than the other platforms, whereas the Ad5-nCov vaccine induced the lowest NAbs response in individuals without a history of COVID-19; therefore, we suggest that a booster could benefit these individuals.

PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico.

Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients.