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Background After millions of years of coevolution, symbiotic microbiota has become an integral part of the host and plays an important role in host immunity, metabolism, and health. Vaccination, as an effective means of preventing infectious diseases, has been playing a vital role in the prevention and control of human and animal diseases for decades. However, so far, minimal is known about the effect of vaccination on fish symbiotic microbiota, especially mucosal microbiota, and its correlation with intestinal metabolism remains unclear. Methods Here we reported the effect of an inactivated bivalent Aeromonas hydrophila / Aeromonas veronii vaccine on the symbiotic microbiota and its correlation with the intestinal metabolism of farmed adult Nile tilapia ( Oreochromis niloticus ) by 16S rRNA gene high-throughput sequencing and gas chromatography-mass spectrometry metabolomics. Results Results showed that vaccination significantly changed the structure, composition, and predictive function of intestinal mucosal microbiota but did not significantly affect the symbiotic microbiota of other sites including gill mucosae, stomach contents, and stomach mucosae. Moreover, vaccination significantly reduced the relative abundance values of potential opportunistic pathogens such as Aeromonas , Escherichia – Shigella , and Acinetobacter in intestinal mucosae. Combined with the enhancement of immune function after vaccination, inactivated bivalent Aeromonas vaccination had a protective effect against the intestinal pathogen infection of tilapia. In addition, the metabolite differential analysis showed that vaccination significantly increased the concentrations of carbohydrate-related metabolites such as lactic acid, succinic acid, and gluconic acid but significantly decreased the concentrations of multiple lipid-related metabolites in tilapia intestines. Vaccination affected the intestinal metabolism of tilapia, which was further verified by the predictive function of intestinal microbiota. Furthermore, the correlation analyses showed that most of the intestinal differential microorganisms were significantly correlated with intestinal differential metabolites after vaccination, confirming that the effect of vaccination on intestinal metabolism was closely related to the intestinal microbiota. Conclusions In conclusion, this paper revealed the microbial and metabolic responses induced by inactivated vaccination, suggesting that intestinal microbiota might mediate the effect of vaccination on the intestinal metabolism of tilapia. It expanded the novel understanding of vaccine protective mechanisms from microbial and metabolic perspectives, providing important implications for the potential influence of vaccination on human intestinal microbiota and metabolism. -tufGxbkxhm-UiFTxxYHNi Video Abstract

Limited follow-up data is available on the recovery of Omicron COVID-19 patients after acute illness. It is also critical to understand persistence of neutralizing antibody (NAb) and of T-cell mediated immunity and the role of hybrid immunity in preventing SARS-CoV-2 reinfection. This prospective cohort study included Omicron COVID-19 individuals from April to June 2022 in Shanghai, China, during a large epidemic caused by the Omicron BA.2 variant. A total of 8945 patients from three medical centres were included in the follow up programme from November 2022 to February 2023. Of 6412 individuals enrolled for the long COVID analysis, 605 (9.4%) individuals experienced at least one sequelae, mainly had fatigue and mental symptoms specific to Omicron BA.2 infection compared with other common respiratory tract infections. During the second-visit, 548 (12.1%) cases of Omicron reinfection were identified. Hybrid immunity with full and booster vaccination had reduced risk of SARS-CoV-2 reinfection by 0.29-fold (95% CI: 0.63-0.81) and 0.23-fold (95% CI: 0.68-0.87), respectively. For 469 participants willing to the hospital during the first visit, those who received full (72 [IQR, 36-156]) or booster (64 [IQR, 28-132]) vaccination had significantly higher neutralizing antibody titers than those with incomplete vaccination (36 [IQR, 16-79]). Moreover, non-reinfection cases had higher neutralizing antibody titers (64 [IQR, 28-152]) compared to reinfection cases (32 [IQR, 20-69]).

We aimed to understand the temporal dynamics of SARS‐CoV‐2 reinfection risk and assess the impact of inactivated vaccination on the occurrence of reinfection. We investigated the reinfection risk of SARS‐CoV‐2 from November 1, 2022, to February 12, 2023, when China rapidly lifted the zero‐COVID policy. The study subjects were those who were first infected during the zero‐COVID period between January 1, 2020, and October 31, 2022, in Dalian city, China. Among the 1961 previous infections, 126 (6.4%, 95% CI: 5.4, 7.5) were reinfected. The risk of reinfection increased over time since initial infection. Compared with those who did not receive or received one dose of inactivated vaccine, receiving two or three doses was associated with additional protection against reinfection among individuals who were infected with pre‐Omicron more than a year earlier, with the OR ranged from 0.33 (95% CI: 0.03, 1.83) to 0.91 (95% CI: 0.22, 3.27). In contrast, no protective effect from two or three doses of vaccines against reinfection was observed among those who were first infected with Omicron variants within a year. Primary or booster vaccination contributed to limited protection against reinfection or symptomatic reinfection among individuals infected with Omicron SARS‐CoV‐2 within a year. However, a booster dose after 1 year of natural infection may provide additional protection against reinfection.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination ( n = 54), one-dose ( n = 62), and two-dose ( n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Background/Objectives: The antibody-dependent enhancement (ADE) of viral entry has been documented for SARS-CoV-2 infection both in vitro and in vivo. However, the potential for the SARS-CoV-2 vaccination to elicit similar ADE effects remains unclear. Methods: In this study, we assessed the in vitro ADE potential of monoclonal antibodies (mAbs) derived from individuals vaccinated with the inactivated SARS-CoV-2 vaccine and compared them to those from one convalescent donor. Results: Our analysis revealed no significant difference in binding affinity or neutralizing capacity between the vaccinated and convalescent mAbs. However, the inactivated SARS-CoV-2 vaccination induced fewer ADE-inducing mAbs, particularly those targeting the Class III epitope on the receptor-binding domain (RBD) compared to those from the convalescent individual. Moreover, no significant in vitro ADE was detected in either vaccinated or convalescent sera, indicating low levels of ADE-inducing antibodies in the sera. Conclusions: An inactivated SARS-CoV-2 vaccination induces fewer ADE-inducing antibodies compared to natural infection, further emphasizing the safety of inactivated SARS-CoV-2 vaccines.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

Additionally, Omicron infection decreased plasmacytoid dendritic cell (pDC) frequencies, which are partially reconstituted after the third dose. [...]there was a shift in the frequency of NK cell subsets, with a decrease in cytokine-secreting CD56hiCD16lo NK cells and an increase in CD56intCD16hi cytotoxic NK cells following three vaccine doses in Omicron-infected individuals. [...]the newly published work enriches our understanding of the immunomodulatory effects of inactivated virus vaccines. [...]we uncover the intricate molecular mechanisms behind the potent antiviral effects induced by three booster doses through ‘trained immunity’.

SARS-CoV-2 vaccination has been reported to be associated with the induction of thyroid disorders. To investigate the influence of SARS-CoV-2 vaccination on the disease course of patients who were undergoing treatment for Graves’ disease (GD), a total of 651 consecutive GD patients who attended follow-up visits in Jiangyuan Hospital were enrolled in this retrospective study, including 443 inactivated SARS-CoV-2 vaccine recipients and 208 unvaccinated participants. The changes in serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and TSH receptor antibody (TRAb) were analyzed. Crude and adjusted hazard ratios (HRs) were estimated using Cox regression models to investigate the risks in incident TRAb positivity and hyperthyroidism recurrence following vaccination. The median levels of TRAb and fT3 significantly decreased in both vaccinated and unvaccinated groups during the GD hyperthyroidism treatment. The fT4 levels of both groups were well within normal limits and presented downward trends simultaneously. Although the present study observed an increasing trend of TSH level during follow-up, significant difference was not seen in both vaccinated and unvaccinated groups. Except for newly diagnosed GD patients, vaccinated participants had significantly lower risks of incident TRAb positivity (adjusted HR = 0.22; 95%CI: 0.10–0.48, P < 0.001) after adjusted for sex, age, disease duration and MMI dose at baseline. Besides, vaccination was unlikely to serve as a risk factor for hyperthyroidism recurrence (adjusted HR = 1.20; 95%CI: 0.51–2.83, P = 0.678). Notably, newly diagnosed patients who received vaccination were just as likely to achieve remission of thyrotoxicosis as those not receiving the vaccination at any time. Our results concluded that inactivated SARS-CoV-2 vaccination would not disturb the treatment course among GD hyperthyroidism patients.

► This study found no association of influenza vaccine with increased occurrence of sickle cell crises in adults. We evaluated the risk of hospitalization for sickle cell crisis (SCC) following influenza vaccination (trivalent inactivated vaccine, TIV) in adults with sickle cell disease. The cohort consisted of all adults aged 18years and older who had a diagnosis of sickle cell disease in the Vaccine Safety Datalink from 1991 to 2006. The outcome measure was any hospitalization for SCC with the main exposure being influenza vaccine. We used a self controlled case series design to compare the incidence rates of hospitalization for SCC during the exposed and unexposed periods after TIV. No significant association between influenza vaccination and hospitalization for sickle cell crisis was found (IRR ratio 0.92, 95% confidence limits 0.66–1.28). These results provide evidence that the seasonal influenza vaccine is safe as recommended in adults who are at high risk for complications of influenza sequelae due to sickle cell disease.

Here, we describe a case of acute disseminated encephalomyelitis (ADEM) that occurred during a plausible risk interval following inactivated influenza vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was treated with intravenous methylprednisolone and immunoglobulin. One-month follow-up revealed resolution of the brain lesions, but not of the spinal cord lesions. No recurrence or progression of the main neurological symptoms was observed. After two years of monitoring, the patient continues to experience weak lower limbs and urinary retention. Thus, we recommend that ADEM should be considered in a patient presenting with neurological symptoms after influenza vaccination.