Impact of sex and age on vaccine-related side effects and their progression after booster mRNA COVID-19 vaccine.

In mRNA COVID-19 vaccination, side effects after the first and second dose have been well reported. However, studies about side effects after booster vaccine are sparse. 272 healthcare workers who received the third mRNA COVID-19 vaccine were recruited, and impact of sex, age, and symptoms on the side effect progression was statistically analyzed. Females and younger adults had a higher frequencies of general fatigue, headache, joint pain, chills and axillary pain compared to males and elderly adults, respectively. In longitudinal analysis, prolonged time to recovery from side effects was found among females and younger adults. Finally, between the third and second dose vaccinations, 52% of subjects had a longer duration of side effects following the third vaccine compared to the second, and joint pain was the culprit symptom related to the prolonged duration of side effects. Following the second vaccine dose, 25% of subjects had a longer duration of side effects and asthma and ear fullness, which exacerbated the underlying allergic condition, and COVID arm symptom were the culprit symptoms. These highlight the impact of sex, age, and culprit symptoms on the progress of side effects following the booster mRNA COVID-19 vaccine.

Impact of Sex and Age on mRNA COVID-19 Vaccine-Related Side Effects in Japan.

mRNA COVID-19 vaccination was initiated worldwide in late 2020, and its efficacy has been well reported. However, studies about vaccine-related side effects are sparse. A total of 262 health care workers who received mRNA COVID-19 vaccine BNT162b2 were recruited, and their vaccine-related side effects were investigated. Impact of sex and age on the side effects was statistically analyzed. A higher number of vaccine-related side effects among females versus males was identified (median 3 versus 2, P < 0.05, after the first dose, and 5 versus 2.5, P < 0.01, after the second dose). General fatigue, headache, chills, and fever were the culprit adverse symptoms. In multivariate analysis, females had an increasing number of side effects after receiving their first (B = 0.7; 95% confidence interval [CI], 0.2 to 1.2) and second (B = 1.5; 95% CI, 0.7 to 2.2) vaccine doses compared to that of males. In age analysis, the older group (≥60 years old) had a lower number of side effects than the younger group (B = -0.5 with a 95% CI of -1.1 to -0.02 after the first vaccine dose, and B = -2.1 with a 95% CI of -2.9 to -1.2 after the second vaccine dose). Additionally, prolonged time to recovery was found among females (P = 0.003 after the first dose; P = 0.008 after the second dose). Specifically, symptoms of general fatigue, headache, itching, swelling at the injection site, and dizziness were the culprit symptoms affecting recovery time. Several cutaneous and membranous symptoms, including "COVID arm," were identified among females. These results highlight the impact of sex and age on side effects from mRNA COVID-19 vaccine and will aid in creating a safer vaccine. IMPORTANCE We demonstrate sex- and age-related impact on mRNA COVID-19 vaccine-related side effects, with a higher number and frequency of side effects and prolonged time to recovery in females compared to males and negative correlation between age and vaccine-related side effects. Identification of unique age- and sex-specific adverse symptoms will provide the opportunity to better understand the nature of sex- and age-associated immunological differences and develop safer and more efficacious vaccines.

Antibodies and Engineered Antibody Fragments against M13 Filamentous Phage to Facilitate Phage-Display-Based Molecular Breeding.

Antibodies are essential for characterizing various analytes. "Molecular-breeding" approaches enable rapid generation of antibody mutants with desirable antigen-binding abilities. Typically, prototype antibodies are converted to single-chain Fv fragments (scFvs), and random mutations are genetically introduced to construct molecular libraries with a vast diversity. Improved species therein are then isolated via phage display genotype-phenotype-connecting systems to separate them from a large excess of nonspecific scFvs. During these experiments, counting of phage particles is routinely performed. However, current methods depend on the time-consuming overnight cultivation of phage-infected bacteria on agar plates to estimate phage numbers as plaque-forming units (pfu) or colony-forming units, the results of which fluctuate considerably. Immunochemical systems capturing phage particles should be a more convenient and robust alternative. We therefore generated monoclonal antibodies against M13 filamentous phage, which is commonly used for phage display, by employing hybridoma technology. Combinatorial use of two such antibodies (Ab-M13#53 and #71; both specific to the major coat protein pVIII) enabled development of a sandwich enzyme-linked immunosorbent assay (ELISA) that could measure ca. 107-1010 phage pfu/mL. To construct a more convenient system, Ab-M13#71 was converted to the scFv form and further fused with an alkaline phosphatase variant. Using this fusion protein, the sandwich ELISA enabled rapid (within 90 min) and reliable phage counting without reducing the sensitivity, and the results were reasonably consistent with those of infection-based methods. The present anti-phage antibodies and scFvs might also enable visualization of individual phage particles by combining them with sensitive fluorescent staining.

Cytochrome p450 induction and gonadal status alteration in common carp (Cyprinus carpio) associated with the discharge of dioxin contaminated effluent to the Hikiji River, Kanagawa Prefecture, Japan.

Accumulations of polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated biphenyls were analyzed in common carp (Cyprinus carpio) collected in the Hikiji River, Kanagawa Prefecture, Japan in which dioxin contaminated effluent was released during the period starting from November 1992 to March 2000. Higher levels of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin toxic equivalents were observed in carps collected downstream to the dioxin release site (contaminated site) than the reference site. Modulations of cytochrome p450 (CYP) enzyme in liver, serum estrogen concentration and gonadal somatic index (GSI) were also measured as biomarkers for the contaminants. Total CYP content in livers was markedly higher in male and female carps from the contaminated site relative to the reference site fish. The expression level of the cytochrome p450 1A and Ethoxyresorufin O-deethylase activity were significantly higher in female carps from the contaminated site than from the reference site. A lower level of plasma estrogen was observed in carps from the contaminated site. The GSI in female carps from the contaminated site was smaller than that recorded at the reference site. The present study indicates that dioxins released to the Hikiji River might induce the CYP enzyme and inhibit the reproductive functions in common carps dwelling downstream from the release site.