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.

Comparative efficacy and acceptability of licensed dose intranasal corticosteroids for moderate-to-severe allergic rhinitis: a systematic review and network meta-analysis.

No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis assessed the comparative efficacy and acceptability of licensed dose aqueous INCSs. PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until 31 March 2022. Eligible studies included randomized controlled trials comparing INCSs with placebo or other types of INCSs in patients with moderate-to-severe allergic rhinitis. Two reviewers independently screened and extracted data following the Preferred Reporting Items in Systematic Reviews and Meta-analysis guideline. A random-effects model was used for data pooling. Continuous outcomes were expressed as standardized mean difference (SMD). The primary outcomes were the efficacy in improving total nasal symptom score (TNSS) and treatment acceptability (the study dropout). We included 26 studies, 13 with 5,134 seasonal AR patients and 13 with 4,393 perennial AR patients. Most placebo-controlled studies had a moderate quality of evidence. In seasonal AR, mometasone furoate (MF) was ranked the highest efficacy, followed by fluticasone furoate (FF), ciclesonide (CIC), fluticasone propionate and triamcinolone acetonide (TAA) (SMD -0.47, 95% CI: -0.63 to -0.31; -0.46, 95% CI: -0.59 to -0.33; -0.44, 95% CI: -0.75 to -0.13; -0.42, 95% CI: -0.67 to -0.17 and -0.41, 95% CI: -0.81 to -0.00), In perennial AR, budesonide was ranked the highest efficacy, followed by FF, TAA, CIC, and MF (SMD -0.43, 95% CI: -0.75 to -0.11; -0.36, 95% CI: -0.53 to -0.19; -0.32, 95% CI: -0.54 to -0.10; -0.29, 95% CI: -0.48 to -0.11; and -0.28, 95% CI: -0.55 to -0.01). The acceptability of all included INCSs was not inferior to the placebo. According to our indirect comparison, some INCSs have superior efficacy to others with moderate quality of evidence in most placebo-controlled studies for treating moderate-to-severe AR.

Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study.

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

COVID-19 Vaccine Hesitancy Among Health Care Workers in Thailand: The Comparative Results of Two Cross-Sectional Online Surveys Before and After Vaccine Availability.

Introduction: The arrival of COVID-19 vaccines in Thailand has supported the fight against the COVID-19 pandemic. This study examined COVID-19 vaccine acceptance among health care workers (HCWs) in Thailand before and after vaccines' availability and investigated factors (both enablers and barriers) affecting their decisions. Methods: Two online self-administered questionnaires were distributed to HCWs in two time-periods: (1) the pre-vaccine arrival period (prior to COVID-19 vaccines' arrival in Thailand, January 28 to February 16, 2021); and (2) the post-vaccine arrival period (April 21 to May 9, 2021). Descriptive analyses and multinomial logistic regression were conducted to examine factors associated with vaccine hesitancy. Results: There were 55,068 respondents in the pre-vaccine arrival period and 27,319 respondents in the post-vaccine arrival period. In the pre-vaccine arrival period, 55.0% of respondents were willing to accept the vaccines, 35.4% were uncertain, and 9.6% declined. In the post-vaccine arrival period, ~16% already received two doses of either the Sinovac or AstraZeneca vaccine, and 43% were administered one dose. Approximately 12% of those who had received the first dose were uncertain or not willing to accept the second dose. Demographic and socio-demographic factors of participants, including their sex, place of residence, and whether they were frontline COVID-19 workers, were found to be the significant factors explaining vaccination hesitancy. Moreover, when comparing the pre-vaccine arrival and post-vaccine arrival periods, it was found that older HCWs were more likely to decline a COVID-19 vaccine in the pre-vaccine arrival period; on the other hand, older HCWs were less likely to decline or be uncertain to receive a COVID-19 vaccine in the post-vaccine arrival period. Conclusion: Information on HCWs' acceptance of COVID-19 vaccines, including who is more likely to accept the vaccines, could assist in planning vaccine allocation to both HCWs and the general public, who often believe HCWs' recommendations. This study's findings set out how policies can be addressed to reduce vaccine hesitancy. This study also highlights HCWs' characteristics (including gender, work region, occupation, and history of receiving influenza vaccination) and the reasons they cited for their vaccine acceptance or hesitance.

Monitoring and Evaluation of National Vaccination Implementation: A Scoping Review of How Frameworks and Indicators Are Used in the Public Health Literature.

An effective Monitoring and Evaluation (M&E) framework helps vaccination programme managers determine progress and effectiveness for agreed indicators against clear benchmarks and targets. We aimed to identify the literature on M&E frameworks and indicators used in national vaccination programmes and synthesise approaches and lessons to inform development of future frameworks. We conducted a scoping review using Arksey and O'Malley's six-stage framework to identify and synthesise sources on monitoring or evaluation of national vaccination implementation that described a framework or indicators. The findings were summarised thematically. We included 43 eligible sources of 4291 screened. Most (95%) were in English and discussed high-income (51%) or middle-income (30%) settings, with 13 in Europe (30%), 10 in Asia-Pacific (23%), nine in Africa (21%), and eight in the Americas (19%), respectively, while three crossed regions. Only five (12%) specified the use of an M&E framework. Most (32/43; 74%) explicitly or implicitly included vaccine coverage indicators, followed by 12 including operational (28%), five including clinical (12%), and two including cost indicators (5%). The use of M&E frameworks was seldom explicit or clearly defined in our sources, with indicators rarely fully defined or benchmarked against targets. Sources focused on ways to improve vaccination programmes without explicitly considering ways to improve assessment. Literature on M&E framework and indicator use in national vaccination programmes is limited and focused on routine childhood vaccination. Therefore, documentation of more experiences and lessons is needed to better inform vaccination M&E beyond childhood.

A systematic review of methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines: Advising resource-constrained settings.

Real-world effectiveness studies are important for monitoring performance of COVID-19 vaccination programmes and informing COVID-19 prevention and control policies. We aimed to synthesise methodological approaches used in COVID-19 vaccine effectiveness studies, in order to evaluate which approaches are most appropriate to implement in low- and middle-income countries (LMICs). For this rapid systematic review, we searched PubMed and Scopus for articles published from inception to July 7, 2021, without language restrictions. We included any type of peer-reviewed observational study measuring COVID-19 vaccine effectiveness, for any population. We excluded randomised control trials and modelling studies. All data used in the analysis were extracted from included papers. We used a standardised data extraction form, modified from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). Study quality was assessed using the REal Life EVidence AssessmeNt Tool (RELEVANT) tool. This study is registered with PROSPERO, CRD42021264658. Our search identified 3,327 studies, of which 42 were eligible for analysis. Most studies (97.5%) were conducted in high-income countries and the majority assessed mRNA vaccines (78% mRNA only, 17% mRNA and viral vector, 2.5% viral vector, 2.5% inactivated vaccine). Thirty-five of the studies (83%) used a cohort study design. Across studies, short follow-up time and limited assessment and mitigation of potential confounders, including previous SARS-CoV-2 infection and healthcare seeking behaviour, were major limitations. This review summarises methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines and highlights the lack of such studies in LMICs, as well as the importance of context-specific vaccine effectiveness data. Further research in LMICs will refine guidance for conducting real-world COVID-19 vaccine effectiveness studies in resource-constrained settings.

Binding and neutralizing antibody levels and vaccine efficacy/effectiveness compared between heterologous and homologous primary series COVID-19 vaccination: A systematic review and meta-analysis.

BACKGROUND: The data on the immunogenicity and efficacy of heterologous primary series COVID-19 vaccination are still limited. OBJECTIVE: To investigate the immunogenicity and vaccine efficacy/effectiveness compared between heterologous and homologous primary series COVID-19 vaccination. METHODS: We conducted a multi-source search for randomized controlled trials, prospective cohort, and case-control studies that investigated the immunogenicity or vaccine efficacy/effectiveness (VE) of heterologous primary series vaccination. Six online databases were searched from inception to June 2022. The primary outcome was the levels of binding antibodies and neutralizing antibodies (NAbs), and the secondary outcomes were VE against COVID-19 infection, hospitalization, and death. RESULTS: Among the 28 included studies, 21 and 7 were included to investigate immunogenicity and VE outcome, respectively. Heterologous CoronaVac (CV)/ChAdOx1 (ChAd) induced higher anti-RBD IgG and NAbs against wild type and delta variants compared to homologous CV or ChAd. However, risk of documented infection of CV/ChAd was similar to homologous CV, but higher than homologous ChAd (odds ratio: 2.56, 95% CI: 1.02-6.37). Heterologous ChAd/BNT162b2 (BNT) elicited a higher anti-spike level than homologous ChAd or BNT, and induced a higher NAbs level against delta variants compared to homologous ChAd. The VE of ChAd/BNT and homologous ChAd or BNT against hospitalization were similar. CONCLUSIONS: Heterologous CV/ChAd induced higher binding and neutralizing antibody levels than homologous CV or ChAd; and, ChAd/BNT induced higher binding and neutralizing antibody levels than homologous ChAd. However, CV/ChAd demonstrated increased risk of infection compared to homologous ChAd. Therefore, immunogenicity findings and real-world vaccine efficacy/effectiveness should be integrated in clinical practice.