Antibody and T-cell response to bivalent booster SARS-CoV-2 vaccines in people with compromised immune function (COVERALL-3).

BACKGROUND: Bivalent mRNA vaccines, designed to combat emerging SARS-CoV-2 variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. METHODS: Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months post vaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/ml (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. RESULTS: In SHCS participants, baseline anti-spike antibody concentrations ≥1642 were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a five-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. CONCLUSIONS: Bivalent mRNA vaccination elicited a robust humoral response in individuals with HIV or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.

Immune responses and reinfection of SARS-CoV-2 Omicron variant in patients with lung cancer.

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection.

A design strategy to generate a SARS-CoV-2 RBD vaccine that abrogates ACE2 binding and improves neutralizing antibody responses.

The structure-based design of antigens holds promise for developing vaccines with higher efficacy and improved safety profiles. We postulate that abrogation of host receptor interaction bears potential for the improvement of vaccines by preventing antigen-induced modification of receptor function as well as the displacement or masking of the immunogen. Antigen modifications may yet destroy epitopes crucial for antibody neutralization. Here, we present a methodology that integrates deep mutational scans to identify and score SARS-CoV-2 receptor binding domain variants that maintain immunogenicity, but lack interaction with the widely expressed host receptor. Single point mutations were scored in silico, validated in vitro, and applied in vivo. Our top-scoring variant receptor binding domain-G502E prevented spike-induced cell-to-cell fusion, receptor internalization, and improved neutralizing antibody responses by 3.3-fold in rabbit immunizations. We name our strategy BIBAX for body-inert, B-cell-activating vaccines, which in the future may be applied beyond SARS-CoV-2 for the improvement of vaccines by design.

SARS-CoV-2 vaccine immunogenicity for people living with HIV: A systematic review and meta-analysis.

BACKGROUND: Previous publications on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) have reported inconsistent results. Additionally, a meta-analysis investigating the immunogenicity in PLWH after the third SARS-CoV-2 vaccine dose is lacking. In this article we aim to provide a systematic review and a meta-analysis studying the immunogenicity of SARS-CoV-2 vaccines in PLWH and to identify potential drivers for antibody response in PLWH. METHODS: We used three databases (PubMed, Embase and Web of Science) to conduct our review. Studies with information on numbers of PLWH producing immunoglobulin G (IgG) antibodies or neutralizing antibodies were included. RESULTS: The meta-analysis included 59 studies and illustrated a pooled serological response of 87.09% in the 10 343 PLWH after they received a SARS-CoV-2 vaccine. High CD4 T-cell counts and low viral load indicated that the study populations had HIV that was well treated, despite varying in location. The pooled effect increased to 91.62% for 8053 PLWH when excluding studies that used inactivated vaccines (BBIBP-CorV and CoronaVac). For the third vaccine dose, the pooled effect was 92.35% for 1974 PLWH. Additionally, weighted linear regression models demonstrated weak relationships between CD4 T-cell count, percentages of people with undetectable HIV load, and age compared with the percentages of PLWH producing a serological response. However, more research is needed to determine the effect of those factors on SARS-CoV-2 vaccine immunogenicity in PLWH. CONCLUSION: SARS-CoV-2 vaccines show a favourable effect on immunogenicity in PLWH. However, the results are not ideal. This meta-analysis suggests that a third SARS-CoV-2 vaccine dose and good HIV treatment procedures are vital to induce a good immunogenicity in PLWH.

The characteristics of BCR-CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccinated volunteers.

The global COVID-19 pandemic has caused more than 1 billion infections, and numerous SARS-CoV-2 vaccines developed rapidly have been administered over 10 billion doses. The world is continuously concerned about the cytokine storms induced by the interaction between SARS-CoV-2 and host, long COVID, breakthrough infections postvaccination, and the impact of SARS-CoV-2 variants. BCR-CDR3 repertoire serves as a molecular target for monitoring the antiviral response "trace" of B cells, evaluating the effects, mechanisms, and memory abilities of individual responses to B cells, and has been successfully applied in analyzing the infection mechanisms, vaccine improvement, and neutralizing antibodies preparation of influenza virus, HIV, MERS, and Ebola virus. Based on research on BCR-CDR3 repertoire of COVID-19 patients and volunteers who received different SARS-CoV-2 vaccines in multiple laboratories worldwide, we focus on analyzing the characteristics and changes of BCR-CDR3 repertoire, such as diversity, clonality, V&J genes usage and pairing, SHM, CSR, shared CDR3 clones, as well as the summary on BCR sequences targeting virus-specific epitopes in the preparation and application research of SARS-CoV-2 potential therapeutic monoclonal antibodies. This review provides comparative data and new research schemes for studying the possible mechanisms of differences in B cell response between SARS-CoV-2 infection or vaccination, and supplies a foundation for improving vaccines after SARS-CoV-2 mutations and potential antibody therapy for infected individuals.

Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis.

BACKGROUND: Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients. RESULTS: This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%. CONCLUSION: While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.

Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus.

OBJECTIVES: We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS). METHODS: Patients aged 12-18 years diagnosed with SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5 mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4 weeks apart, followed by a booster (third) dose at 4-6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored. RESULTS: A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4 weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups (p = .498). AdoSLE on High-IS had lower anti-RBD IgG (p < .001), Wuhan NT (p < .001), and IFN-γ-ELISpot (p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose (p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12 weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups. CONCLUSION: AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.

A single-center review of outcomes between COVID-19 vaccinated and unvaccinated liver transplant recipients.

BACKGROUND: With the availability of vaccines against SARS-COV-2, recommendations for vaccination of transplant candidates are widespread. At our institution, patients may receive liver transplant (LTx) regardless of vaccine status. The purpose of this study is to compare post-LTx outcomes between vaccinated (VAX) and unvaccinated (UNVAX) LTx recipients. METHODS: This is a retrospective, single-center study of LTx from January 1, 2021-March 30, 2022. The primary outcome is incidence of post-LTx COVID-19. Secondary outcomes include graft function, mortality, graft loss, and COVID-19 treatment. RESULTS: One hundred and seventy-seven LTx recipients were included, 57% [101/177] VAX and 43% [76/177] UNVAX. Baseline characteristics were similar between groups. Overall, 28 (36.8%) UNVAX and 34 (33.7%) VAX tested COVID-19 positive during the study period (p = .193) at a mean of 312.6 [255.4-369.8] days for UNVAX versus 254.6 [215.2-293.9] days for VAX (p = .084). COVID-19 treatment was administered in 15 (53.6%) of the UNVAX compared to 22 (64.7%) in the VAX (p = .374), although eight (28.6%) of UNVAX required hospital admission for treatment compared with two (5.9%) of VAX (p = .016). There were no statistically significant differences in death, and no COVID-19 related death or graft loss. There were no statistically significant differences in liver function tests at 3- and 12-months post LTx. CONCLUSION: In a series with a large percentage of UNVAX patients, LTx appears to be safe, with no difference in the rate of COVID-19 or transplant-related outcomes compared to VAX. While we encourage vaccination to prevent severe COVID, based on our results, vaccine status should not be reason to deny lifesaving transplant.

SARS-CoV-2 Vaccination Rates and Uptake of Tixagevimab-Cilgavimab Among a Cohort of Pediatric Solid Organ Transplant Recipients.

INTRODUCTION: There is a lack of data regarding SARS-CoV-2 vaccination rates and tixagevimab-cilgavimab (TC) uptake among pediatric solid organ transplant recipients. The purpose of our study was to assess these rates. MATERIALS AND METHODS: We reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN, who received a transplant between January 2011 and December 2021. All SARS-CoV-2 vaccines and doses of TC received on or before September 1, 2022, the date of approval of the bivalent SARS-CoV2 vaccine, were included. We also assessed whether patients had been seen by an infectious diseases physician (ID) in the preceding 6 months. RESULTS: Our study included 110 patients: 47 kidney, 36 heart, and 27 liver transplant recipients. All vaccine doses recorded were monovalent SARS-CoV-2 vaccines. Sixty-eight (61.8%) patients received at least one vaccine. This varied by age group, with f of ≥12 years olds, 40.9% of 5-11 year olds and 14.3% of under 5 year olds (p = 0.001). Seven patients (6.4%) were up-to-date (UTD) for age. There was no difference in UTD status by organ type (p = 0.335). Patients who saw ID were significantly more likely to be UTD (13.2% versus 2.8%; p = 0.047). Among those eligible, 14 (18.2%) received TC, with rates not different based on transplanted organ type (p = 0.158) or whether they saw ID (p = 0.273). CONCLUSIONS: Despite the availability of vaccines, nearly 40% of pediatric solid organ transplant recipients remained unvaccinated against SARS-CoV-2 at time of the bivalent vaccine release. Less than a fifth of eligible patients received TC. Strategies to increase uptake of SARS-CoV-2 vaccines as well as adjunctive agents among this vulnerable group should be further explored.

Arginine vasopressin deficiency onset after COVID-19 vaccination with positive anti-rabphilin-3A antibodies: a case report and literature review.

BACKGROUND: Arginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases. CASE PRESENTATION: A 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed. CONCLUSION: We experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination.

Association between use of antipyretics and antibody titers after two doses of the BNT162b2 SARS-CoV-2 vaccine in adolescents and young adults with underlying diseases.

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (ß coefficient [95% CI] = -0.107 [-0.438 to 0.224]).

A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike.

The current pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters. We found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2-specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent. Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response. The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, body weight loss, cytokine storm, and lung pathology. These data demonstrate that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine.

Relative Effectiveness of Coronavirus Disease 2019 Vaccination and Booster Dose Combinations Among 18.9 Million Vaccinated Adults During the Early Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Period-United States, 1 January 2022 to 31 March 2022.

BACKGROUND: Small sample sizes have limited prior studies' ability to capture severe COVID-19 outcomes, especially among Ad26.COV2.S vaccine recipients. This study of 18.9 million adults aged ≥18 years assessed relative vaccine effectiveness (rVE) in three recipient cohorts: (1) primary Ad26.COV2.S vaccine and Ad26.COV2.S booster (2 Ad26.COV2.S), (2) primary Ad26.COV2.S vaccine and mRNA booster (Ad26.COV2.S+mRNA), (3) two doses of primary mRNA vaccine and mRNA booster (3 mRNA). METHODS: We analyzed two de-identified datasets linked using privacy-preserving record linkage (PPRL): insurance claims and retail pharmacy COVID-19 vaccination data. We assessed the presence of COVID-19 diagnosis during January 1-March 31, 2022 in: (1) any claim, (2) outpatient claim, (3) emergency department (ED) claim, (4) inpatient claim, and (5) inpatient claim with intensive care unit (ICU) admission. rVE for each outcome comparing three recipient cohorts (reference: two Ad26.COV2.S doses) was estimated from adjusted Cox proportional hazards models. RESULTS: Compared with two Ad26.COV2.S doses, Ad26.COV2.S+mRNA and three mRNA doses were more effective against all COVID-19 outcomes, including 57% (95% CI: 52-62) and 62% (95% CI: 58-65) rVE against an ED visit; 44% (95% CI: 34-52) and 54% (95% CI: 48-59) rVE against hospitalization; and 48% (95% CI: 22-66) and 66% (95% CI: 53-75) rVE against ICU admission, respectively. CONCLUSIONS: This study demonstrated that Ad26.COV2.S + mRNA doses were as good as three doses of mRNA, and better than two doses of Ad26.COV2.S. Vaccination continues to be an important preventive measure for reducing the public health impact of COVID-19.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Effects of inactivated SARS-CoV-2 vaccination on male fertility: A retrospective cohort study.

Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID-19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID-19 mRNA vaccine since then but have come up with conflicting results. As a near-ideal candidate for mass immunization programs, inactivated SARS-CoV-2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility. Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. Five hundred and nineteen fertile men with no history of laboratory-confirmed COVID-19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n = 168), one-dose vaccinated group (n = 8), fully vaccinated group (n = 183), and booster group (n = 160). All of them underwent a semen analysis and most had serum sex hormone levels tested. There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination-to-test interval-specific changes, sub-analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased follicle-stimulating hormone level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID-19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened. Our study suggests that inactivated SARS-CoV-2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccines in people living with HIV: A longitudinal cohort study.

To clarify the characteristics in immunogenicity and safety of inactivated SARS-Cov-2 vaccines among HIV-infected individuals, a longitudinal cohort study was performed on HIV-infected and HIV-uninfected participants with no history of COVID-19 infection and COVID-19 vaccine inoculation. Participants information and adverse events were collected. Blood samples were collected on the same day before vaccination, 21 days after the first shot, 28 days after the second shot, 6 months after the second vaccination and 14 days after the third dose to test anti-receptor-binding domain IgG antibody, viral load, CD4+, CD8+ T cell count. Our result showed that although HIV-infected adults with low nadir CD4+ T cell count ≤ 350 cells/mm3 generate significantly lower immune response after three shots of vaccine compared with HIV-negative controls, 100% of all the HIV-infected and healthy controls were seroconverted after the third shot. Seroconversion ratio and antibody level of 190 days after two shots of vaccination for HIV-infected with nadir CD4+ T cell count ≤ 350 were significantly lower than that of healthy controls. No significant difference was found in viral load among blood samples collected at each time points. CD4 and CD4/CD8 ratio value were found increased greatly after each shot of inoculation in HIV-infected individuals with nadir CD4+ T cell count ≤ 350. Multiple logistic regression analysis showed that among HIV-infected individuals, PLWH with CD4+ T cell count ≤ 350 were less likely experience seroconversion 21 days after the first shot, and less likely maintained antibody immunity 6 months post 2nd dose. Adverse events after each inoculation were not serious and recovered within 1 week. In conclusion, inactivated COVID-19 vaccine was safe and effective in people living with HIV after three shots of vaccination. HIV-infected individuals with low nadir CD4+ T cell count ≤ 350 was associated with a nonoptimal antibody response. Further vaccination strategies could be developed for those with low CD4+ T cell counts.

Development of SARS-CoV-2 animal vaccines using a stable and efficient NDV expression system.

With the continuation of the coronavirus disease 2019 pandemic and the emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, the control of the spread of the virus remains urgent. Various animals, including cats, ferrets, hamsters, nonhuman primates, minks, tree shrews, fruit bats, and rabbits, are susceptible to SARS-CoV-2 infection naturally or experimentally. Therefore, to avoid animals from becoming mixing vessels of the virus, vaccination of animals should be considered. In the present study, we report the establishment of an efficient and stable system using Newcastle disease virus (NDV) as a vector to express SARS-CoV-2 spike protein/subunit for the rapid generation of vaccines against SARS-CoV-2 in animals. Our data showed that the S and S1 protein was sufficiently expressed in rNDV-S and rNDV-S1-infected cells, respectively. The S protein was incorporated into and displayed on the surface of rNDV-S viral particles. Intramuscular immunization with rNDV-S was found to induce the highest level of binding and neutralizing antibodies, as well as strong S-specific T-cell response in mice. Intranasal immunization with rNDV-S1 provoked a robust T-cell response but barely any detectable antibodies. Overall, the NDV-vectored vaccine candidates were able to induce profound humoral and cellular immunity, which will provide a good system for developing vaccines targeting both T-cell and antibody responses.

Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Vaccine-Associated Uveitis after COVID-19 Vaccination: Vaccine Adverse Event Reporting System Database Analysis.

PURPOSE: To assess the risk of vaccine-associated uveitis (VAU) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and evaluate uveitis onset interval and clinical presentations in the patients. DESIGN: A retrospective study from December 11, 2020, to May 9, 2022, using the Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. PARTICIPANTS: Patients diagnosed with VAU after administration of BNT162b2 (Pfizer-BioNTech, Pfizer Inc/BioNTech SE), mRNA-1273 (Moderna, Moderna Therapeutics Inc), and Ad26.COV2.S (Janssen, Janssen Pharmaceuticals) vaccine worldwide. METHODS: A descriptive analysis of the demographics, clinical history, and presentation was performed. We evaluated the correlation among the 3 vaccines and continuous and categorical variables. A post hoc analysis was performed between uveitis onset interval after vaccination and age, dose, and vaccine type. Finally, a 30-day risk analysis for VAU onset postvaccination was performed. MAIN OUTCOME MEASURES: The estimated global crude reporting rate, observed to expected ratio of VAU in the United States, associated ocular and systemic presentations, and onset duration. RESULTS: A total of 1094 cases of VAU were reported from 40 countries with an estimated crude reporting rate (per million doses) of 0.57, 0.44, and 0.35 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The observed to expected ratio of VAU was comparable for BNT162b2 (0.023), mRNA-1273 (0.025), and Ad26.COV2.S (0.027). Most cases of VAU were reported in patients who received BNT162b2 (n = 853, 77.97%). The mean age of patients with VAU was 46.24 ± 16.93 years, and 68.65% (n = 751) were women. Most cases were reported after the first dose (n = 452, 41.32%) and within the first week (n = 591, 54.02%) of the vaccination. The onset interval for VAU was significantly longer in patients who received mRNA-1273 (21.22 ± 42.74 days) compared with BNT162b2 (11.42 ± 23.16 days) and rAd26.COV2.S (12.69 ± 16.02 days) vaccines (P < 0.0001). The post hoc analysis revealed a significantly shorter interval of onset for the BNT162b2 compared with the mRNA 1273 vaccine (P < 0.0001). The 30-day risk analysis showed a significant difference among the 3 vaccines (P < 0.0001). CONCLUSIONS: The low crude reporting rate and observed to expected ratio suggest a low safety concern for VAU. This study provides insights into a possible temporal association between reported VAU events and SARS-CoV-2 vaccines; however, further investigations are required to delineate the associated immunological mechanisms.

The Presence of Lung Cancer Affects SARS-CoV-2 Vaccine Uptake and Attitude in Chinese Patients: A Clinical Cross-Sectional Investigation.

With the SARS-CoV-2 mutations evolving and prompt of SARS-CoV-2 vaccines, no information is available on SARS-CoV-2 vaccination status in Chinese patients with lung cancer. An electronic questionnaire including sociodemographic characteristics, vaccine status, side effect post-vaccination, and attitude towards a fourth dose of vaccine was conducted within 1018 Chinese patients with lung cancer from October 18th, 2022, to November 25th, 2022. Among 1018 patients, a total of 75 (13.7%) patients reported acceptable systemic adverse events in those had received the SARS-CoV-2 vaccine (549, 54%), the most common of which was fever (39, 7%). Factors including females (OR, 1.512; 95% CI, 1.076-2.124), residents in the municipality (OR, 2.048; 95% CI, 1.238-3.389), undergoing therapy (OR, 2.897; 95% CI, 1.348-6.226), disagree to vaccines is safe for patients with lung cancer (OR, 3.816; 95% CI, 2.198-6.626) contributed to hesitancy. Among 373 patients had received three doses, half respondents (206, 55.2%) were hesitant to receive a fourth dose due to the safety concern and efficacy towards the variants. In conclusion, low vaccine uptake rates in patients with lung cancer could be improved by increasing confidence in vaccine safety, particularly for those with negative beliefs. Appropriate guidance and individualized vaccination plans that meet the healthcare needs of patients with lung cancer were needed during the constantly evolving pandemic.