Indirect vaccine effectiveness in an outbreak of Alpha B.1.1.7 variant in a California state Prison, May 2021.

Incarcerated populations experienced high rates of SARS-CoV-2 infection and death during early phases of the COVID-19 pandemic. To evaluate vaccine effectiveness in the carceral context, we investigated the first outbreak of COVID-19 in a California state prison following widespread rollout of vaccines to residents in early 2021. We identified a cohort of 733 state prison residents presumed to be exposed between May 14 and June 22, 2021. 46.9 % (n = 344) were vaccinated, primarily with two doses of mRNA-1273 (n = 332, 93.6 %). In total, 92 PCR-positive cases were identified, of which 14 (14.5 %) occurred among mRNA-1273 vaccinated residents. No cases required hospitalization. All nine isolates collected belonged to the Alpha (B.1.1.7) variant. We used Cox proportional hazard regression to estimate vaccine effectiveness for at least one dose of any vaccine at the start of the outbreak. Vaccine effectiveness was 86 % (95 % CI: 75 %-97 %) against PCR-confirmed infection, with similar results for symptomatic infection. Higher rates of building-level vaccine uptake were associated with a lower overall rate of PCR-confirmed infection and symptomatic infection among unvaccinated residents. Among unvaccinated residents who lived in shared cells at the time of presumed exposure, exposure to a vaccinated cellmate was associated with a 38% (95% CI: 0.37, 1.04) lower hazard rate of PCR-confirmed infection over the study period. In this outbreak involving the Alpha SARS-CoV-2 variant, vaccination conferred direct and possibly indirect protection against SARS-CoV-2 infection and symptomatic COVID-19. Our results support the importance of vaccine uptake in mitigating outbreaks and severe disease in the prison setting and the consideration of community vaccination levels in policy and infection response.

Evaluation of vaccine effectiveness of mRNA COVID-19 vaccines in children: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the vaccine effectiveness (VE) of mRNA COVID-19 vaccines in children using a meta-analysis approach. MATERIALS AND METHODS: Relevant studies on the use of mRNA COVID-19 vaccines in children were identified through computerized searches. VE-related indicators were extracted, and data analysis was performed using the R software with the meta-package. RESULTS: This study included a total of 12 relevant articles involving 9,963,732 participants from multiple centers in different countries, including the United States, Canada, Singapore, Israel, South Korea, and Qatar. The administered vaccine types included BNT162b2 and mRNA-1273. Participants were categorized into partially immunized (one dose of vaccine) and fully immunized (two doses of vaccine). Four articles reported VE after one dose of vaccine, while 12 reported VE after two doses. Heterogeneity analysis indicated significant heterogeneity among the studies, warranting the use of a random-effects model for analysis. Meta-analysis results revealed that the VE of partial immunization ranged from 16.61 (95% CI: 6.32-25.77) to 34.30 (95% CI: 24.21-43.04), with a pooled VE of 22.80 (95% CI: 15.68-29.32). The VE after full immunization ranged from 16.14 (95% CI: 14.42-17.83) to 90.47 (95% CI: 67.42-97.21), with a pooled VE of 56.17 (95% CI: 41.12-67.37). Meta-regression analysis showed no statistically significant correlation between VE and time (p>0.05). CONCLUSIONS: Both partial and full immunization of the BNT162b2 mRNA vaccine provide benefits in reducing infection rates. VE varies over time and is closely associated with viral mutations and waning immunity. The specific mechanisms require further investigation.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Relative Effectiveness of the MF59®-Adjuvanted Influenza Vaccine Versus High-Dose and Non-Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019-2020 US Influenza Season.

BACKGROUND: Adults ≥ 65 years of age have suboptimal influenza vaccination responses compared to younger adults due to age-related immunosenescence. Two vaccines were specifically developed to enhance protection: MF59-adjuvanted trivalent influenza vaccine (aIIV3) and high-dose egg-based trivalent influenza vaccine (HD-IIV3e). METHODS: In a retrospective cohort study conducted using US electronic medical records linked to claims data during the 2019-2020 influenza season, we compared the relative vaccine effectiveness (rVE) of aIIV3 with HD-IIV3e and a standard-dose non-adjuvanted egg-based quadrivalent inactivated influenza vaccine (IIV4e) for the prevention of cardiorespiratory hospitalizations, including influenza hospitalizations. We evaluated outcomes in the "any" diagnosis position and the "admitting" position on the claim. A doubly robust methodology using inverse probability of treatment weighting and logistic regression was used to adjust for covariate imbalance. rVE was calculated as 100 * (1 - ORadjusted). RESULTS: The study included 4,299,594 adults ≥ 65 years of age who received aIIV3, HD-IIV3e, or IIV4e. Overall, aIIV3 was associated with lower proportions of cardiorespiratory hospitalizations with diagnoses in any position compared to HD-IIV3e (rVE = 3.9% [95% CI, 2.7-5.0]) or IIV4e (9.0% [95% CI, 7.7-10.4]). Specifically, aIIV3 was more effective compared with HD-IIV3e and IIV4e in preventing influenza hospitalizations (HD-IIV3e: 9.7% [95% CI, 1.9-17.0]; IIV4e: 25.3% [95% CI, 17.7-32.2]). Consistent trends were observed for admitting diagnoses. CONCLUSION: Relative to both HD-IIV3e and IIV4e, aIIV3 provided improved protection from cardiorespiratory or influenza hospitalizations.

Impact of SARS-CoV-2 vaccines on Covid-19 incidence and mortality in the United States.

BACKGROUND: Given the waning of vaccine effectiveness and the shifting of the most dominant strains in the U.S., it is imperative to understand the association between vaccination coverage and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease and mortality at the community levels and whether that association might vary according to the dominant SARS-CoV-2 strains in the U.S. METHODS: Generalized estimating equations were used to estimate associations between U.S. county-level cumulative vaccination rates and booster distribution and the daily change in county-wide Coronavirus 2019 disease (COVID-19) risks and mortality during Alpha, Delta and Omicron predominance. Models were adjusted for potential confounders at both county and state level. A 2-week lag and a 4-week lag were introduced to assess vaccination rate impact on incidence and mortality, respectively. RESULTS: Among 3,073 counties in 48 states, the average county population complete vaccination rate of all age groups was 50.79% as of March 11th, 2022. Each percentage increase in vaccination rates was associated with reduction of 4% (relative risk (RR) 0.9607 (95% confidence interval (CI): 0.9553, 0.9661)) and 3% (RR 0.9694 (95% CI: 0.9653, 0.9736)) in county-wide COVID-19 cases and mortality, respectively, when Alpha was the dominant variant. The associations between county-level vaccine rates and COVID-19 incidence diminished during the Delta and Omicron predominance. However, each percent increase in people receiving a booster shot was associated with reduction of 6% (RR 0.9356 (95% CI: 0.9235, 0.9479)) and 4% (RR 0.9595 (95% CI: 0.9431, 0.9761)) in COVID-19 incidence and mortality in the community, respectively, during the Omicron predominance. CONCLUSIONS: Associations between complete vaccination rates and COVID-19 incidence and mortality appeared to vary with shifts in the dominant variant, perhaps due to variations in vaccine efficacy by variant or to waning vaccine immunity over time. Vaccine boosters were associated with notable protection against Omicron disease and mortality.

The effect of COVID-19 vaccine to the Omicron variant in children and adolescents: a systematic review and meta-analysis.

Background: Omicron (B.1.1.529), a variant of SARS-CoV-2, has emerged as a dominant strain in COVID-19 pandemic. This development has raised concerns about the effectiveness of vaccination to Omicron, particularly in the context of children and adolescents. Our study evaluated the efficacy of different COVID-19 vaccination regimens in children and adolescents during the Omicron epidemic phase. Methods: We searched PubMed, Cochrane, Web of Science, and Embase electronic databases for studies published through March 2023 on the association between COVID-19 vaccination and vaccine effectiveness (VE) against SARS-CoV-2 infection in children and adolescents at the Omicron variant period. The effectiveness outcomes included mild COVID-19 and severe COVID-19. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered in PROSPERO (CRD42023390481). Results: A total of 33 studies involving 16,532,536 children were included in the analysis. First, in children and adolescents aged 0-19 years, the overall VE of the COVID-19 vaccine is 45% (95% confidence interval [CI]: 40 to 50%). Subgroup analysis of VE during Omicron epidemic phase for different dosage regimens demonstrated that the VE was 50% (95% CI: 44 to 55%) for the 2-dose vaccination and 61% (95% CI: 45 to 73%) for the booster vaccination. Upon further analysis of different effectiveness outcomes during the 2-dose vaccination showed that the VE was 41% (95% CI: 35 to 47%) against mild COVID-19 and 71% (95% CI: 60 to 79%) against severe COVID-19. In addition, VE exhibited a gradual decrease over time, with the significant decline in the efficacy of Omicron for infection before and after 90 days following the 2-dose vaccination, registering 54% (95% CI: 48 to 59%) and 34% (95% CI: 21 to 56%), respectively. Conclusion: During the Omicron variant epidemic, the vaccine provided protection against SARS-CoV-2 infection in children and adolescents aged 0-19 years. Two doses of vaccination can provide effective protection severe COVID-19, with booster vaccination additionally enhancing VE.

How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

Introduction: The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. Methods: A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. Results: The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Conclusion: Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

Safety, immunogenicity, and protective effective of inhaled COVID-19 vaccines: A systematic review and meta-analysis.

This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta-analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb-GMT) with aerosolised Ad5-nCoV (AAd5-nCoV) were all higher than those with inactivated vaccine (INA-nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96-2.69) and intramuscular Ad5-nCoV (IMAd5-nCoV) (SMD = 0.31; 95% CI: 0.14-0.48) against the original strain of SARS-CoV-2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5-nCoV compared to INA-nCoV or IMAd5-nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5-nCoV had a high immune response (including mucosal immunity) and provided protection against COVID-19 caused by the SARS-CoV-2 omicron variant. Further studies are needed to investigate the long-term safety of intranasal vaccine booster protection and various types of ICVs.

Immunogenicity and safety of live attenuated and recombinant/inactivated varicella zoster vaccines in people living with HIV: A systematic review.

Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.

Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Immunocompromised individuals are at increased risk of COVID-19 breakthrough infection, hospitalization, and death in the post-vaccination era: A systematic review.

INTRODUCTION: Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the postvaccination era, immunocompromised individuals remain at high risk of breakthrough infection and COVID-19 related hospitalization and death, which persist despite vaccination efforts. There has been a marked paucity of systematic reviews evaluating existing data describing the clinical measures of efficacy of COVID-19 vaccination, specifically in immunocompromised populations. In particular, there is a scarcity of comprehensive evaluations exploring breakthrough infections and severe COVID-19 in this patient population. METHODS: To address this gap, we conducted a systematic review which aimed to provide a summary of current clinical evidence of the effectiveness of COVID-19 vaccination in the immunocompromised population. Using PRISMA guidelines, we conducted a literature search on PubMed and the Cochrane database published between January 1, 2021 to September 1, 2022. RESULTS: Our findings demonstrated that despite vaccination, immunocompromised patients remained at high risk of new breakthrough COVID-19 infection and severe COVID-19 outcomes compared to the general population. We found increased average relative risk (RR) of breakthrough infections in the immunocompromised population, including patients with cancer (RR = 1.4), HIV (RR = 1.92), chronic kidney disease (RR = 2.26), immunodeficiency (RR = 2.55), and organ transplant recipients (RR = 6.94). These patients are also at greater risk for hospitalizations and death following COVID-19 breakthrough infection. We found that the RR of hospitalization and death in Cancer patients was 1.08 and 2.82, respectively. CONCLUSION: This demonstrated that vaccination does not offer an adequate level of protection in these groups, necessitating further measures such as Evusheld and further boosters.

Effectiveness of XBB.1.5 Monovalent COVID-19 Vaccines During a Period of XBB.1.5 Dominance in EU/EEA Countries, October to November 2023: A VEBIS-EHR Network Study.

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in booster-eligible ≥ 65-year-olds, during October-November 2023. We linked electronic records to construct retrospective cohorts and used Cox models to estimate adjusted hazard ratios and derive VE. VE for COVID-19 hospitalisation and death was, respectively, 67% (95%CI: 58-74) and 67% (95%CI: 42-81) in 65- to 79-year-olds and 66% (95%CI: 57-73) and 72% (95%CI: 51-85) in ≥ 80-year-olds. Results indicate that periodic vaccination of individuals ≥ 65 years has an ongoing benefit and support current vaccination strategies in the EU/EEA.

Evolution of the data and methods in real-world COVID-19 vaccine effectiveness studies on mortality: a scoping review protocol.

BACKGROUND: Early evidence on COVID-19 vaccine efficacy came from randomised trials. Many important questions subsequently about vaccine effectiveness (VE) have been addressed using real-world studies (RWS) and have informed most vaccination policies globally. As the questions about VE have evolved during the pandemic so have data, study design, and analytical choices. This scoping review aims to characterise this evolution and provide insights for future pandemic planning-specifically, what kinds of questions are asked at different stages of a pandemic, and what data infrastructure and methods are used? METHODS AND ANALYSIS: We will identify relevant studies in the Johns Hopkins Bloomberg School of Public Health VIEW-hub database, which curates both published and preprint VE RWS identified from PubMed, Embase, Scopus, Web of Science, the WHO COVID Database, MMWR, Eurosurveillance, medRxiv, bioRxiv, SSRN, Europe PMC, Research Square, Knowledge Hub, and Google. We will include RWS of COVID-19 VE that reported COVID-19-specific or all-cause mortality (coded as 'death' in the 'effectiveness studies' data set).Information on study characteristics; study context; data sources; design and analytic methods that address confounding will be extracted by single reviewer and checked for accuracy and discussed in a small group setting by methodological and analytic experts. A timeline mapping approach will be used to capture the evolution of this body of literature.By describing the evolution of RWS of VE through the COVID-19 pandemic, we will help identify options for VE studies and inform policy makers on the minimal data and analytic infrastructure needed to support rapid RWS of VE in future pandemics and of healthcare strategies more broadly. ETHICS AND DISSEMINATION: As data is in the public domain, ethical approval is not required. Findings of this study will be disseminated through peer-reviewed publications, conference presentations, and working-papers to policy makers. REGISTRATION: https://doi.org/10.17605/OSF.IO/ZHDKR.

Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection.

BACKGROUND: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines. RESEARCH DESIGN AND METHODS: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination. RESULTS: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains. CONCLUSIONS: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

Influenza and COVID-19 co-infection and vaccine effectiveness against severe cases: a mathematical modeling study.

Background: Influenza A virus have a distinctive ability to exacerbate SARS-CoV-2 infection proven by in vitro studies. Furthermore, clinical evidence suggests that co-infection with COVID-19 and influenza not only increases mortality but also prolongs the hospitalization of patients. COVID-19 is in a small-scale recurrent epidemic, increasing the likelihood of co-epidemic with seasonal influenza. The impact of co-infection with influenza virus and SARS-CoV-2 on the population remains unstudied. Method: Here, we developed an age-specific compartmental model to simulate the co-circulation of COVID-19 and influenza and estimate the number of co-infected patients under different scenarios of prevalent virus type and vaccine coverage. To decrease the risk of the population developing severity, we investigated the minimum coverage required for the COVID-19 vaccine in conjunction with the influenza vaccine, particularly during co-epidemic seasons. Result: Compared to the single epidemic, the transmission of the SARS-CoV-2 exhibits a lower trend and a delayed peak when co-epidemic with influenza. Number of co-infection cases is higher when SARS-CoV-2 co-epidemic with Influenza A virus than that with Influenza B virus. The number of co-infected cases increases as SARS-CoV-2 becomes more transmissible. As the proportion of individuals vaccinated with the COVID-19 vaccine and influenza vaccines increases, the peak number of co-infected severe illnesses and the number of severe illness cases decreases and the peak time is delayed, especially for those >60 years old. Conclusion: To minimize the number of severe illnesses arising from co-infection of influenza and COVID-19, in conjunction vaccinations in the population are important, especially priority for the elderly.

Predicting Vaccine Effectiveness for Hospitalization and Symptomatic Disease for Novel SARS-CoV-2 Variants Using Neutralizing Antibody Titers.

The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8-4.4-fold and increased the risk of symptomatic disease 1.7-4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants.

Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients.

Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis.

Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (TRM), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These TRM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4+ TRM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4+ TRM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4+ TRM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania-specific memory CD4+ T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4+ TRM cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4+ TRM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.