Measure Of Vaccine Efficacy Research Articles

Development a high-sensitivity sandwich ELISA for determining antigen content of porcine circovirus type 2 vaccines

Porcine circovirus type 2 (PCV2) is intensely prevalent in global pig farms. The PCV2 vaccine is an important means of preventing and controlling PCV2. The quality control of PCV2 vaccines is predominantly based on detection techniques such as animal testing and neutralizing antibody titration. Measuring the content of effective proteins in vaccines to measure vaccine efficacy is an excellent alternative to traditional methods, which can greatly accelerate the development speed and testing time of vaccines. In this study, we screened a monoclonal antibody (mAb) that can effectively recognize not only the exogenous expression of PCV2 Cap protein but also PCV2 virus. The double antibody sandwich ELISA (DAS-ELISA) was developed using this mAb that specifically recognize PCV2 Cap. The minimum protein content detected by this method is 3.5 ng/mL. This method can be used for the quality control of PCV2 inactivated vaccine and subunit vaccine, and the detection results are consistent with the results of mice animal experiments. This method has the advantages of simple operation, good sensitivity, high specificity and wide application. It can detect the effective antigen Cap protein content of various types of PCV2 vaccines, which not only shorten the vaccine inspection time but also save costs.

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

Humoral and Cell-Mediated Responses to SARS-CoV-2 Vaccination in a Cohort of Immunodeficient Patients.

This study delves into the intricate landscape of SARS-CoV-2 vaccine response in immunodeficient patients, focusing on the dynamics of both humoral and cell-mediated immunity. The cohort includes patients with common variable immunodeficiency (CVI), agammaglobulinemia (XLA), and combined immunodeficiency (CI). The findings reveal varying degrees of antibody production, with XLA patients exhibiting no measurable response but displaying a robust T-cell-mediated response. The study emphasizes the importance of considering both arms of the immune system in assessing vaccine immunogenicity, particularly in the context of immunodeficiency. The results challenge conventional measures of vaccine efficacy only based on antibody titers, highlighting the need for a more comprehensive understanding of the immune response in this vulnerable population. This research contributes valuable insights to guide clinical decisions regarding vaccination strategies, booster doses, and overall protection in immunodeficient individuals.

Sialophorin is an essential host element for vaccine immunity against pulmonary fungal infections

Abstract The global incidence of fungal infections is alarming due to the increasing immunocompromised population. Vaccine measures are necessary to prevent fungal diseases. Identifying a protective host element as a functional phenotypic marker is immensely valuable as a target to enhance vaccine responses, measure vaccine efficacy, and assess disease outcomes. We identified a host element, O-glycosylated sialophorin, preferentially associated with antifungal memory Tc17 (IL-17A +) cells. Using a mouse model of fungal vaccine immunity during CD4 +T-cell deficiency, we found that sialophorin was essential to bolster vaccine-induced CD8 +T-cell responses and immunity to pulmonary infection. Sialophorin-sufficient CD8 +T cells were superior in responses than the deficient cells under a similar inflammatory micromilieu. Supplementation of sialophorin mAb that binds to O-glycosylated form potentiated the CD8 +T cell responses to fungal antigens, and an inhibitory mAb that binds to non-O-glycosylated form selectively reduced Tc1 (IFNγ +) but not Tc17 cell responses. Sialophorin-mediated immunity was independent of T cell trafficking into the lung. Finally, using fungal antigens vaccination, we show that O-glycosylated sialophorin is a marker of vaccine-potency and immunity. Our study revealed that sialophorin is an essential host element to bolster vaccine responses and serves as a potential biomarker of fungal immunity. NIAID-NIH 5R01AI153522

Nano-Encapsulated Antioxidant: Retinoic Acid as a Natural Mucosal Adjuvant for Intranasal Immunization against Chronic Experimental Toxoplasmosis

The tight relationship between immunity and retinoid levels provides evidence on the critical role of retinoic acid (RA) in regulating immune activity, especially the mucosal one. Mucosal immune response is the key for determination of the outcome of infection, particularly against intracellular mucosal pathogens such as Toxoplasma gondii, where it plays a crucial role as a sentinel against parasite invasion. Herein, the immunomodulatory adjuvant role of RA was evaluated for prophylactic vaccination against chronic Toxoplasma infection. A quantity of 15 µg of RA pre-encapsulated with lipid-based nanoparticles (SLNs) was intranasally used in three doses, two weeks apart, as an adjuvant to the Toxoplasma lysate antigen (TLA). Afterward, mice were infected with 20 cysts of T. gondii (ME49 strain) and were sacrificed at the 4th week post-infection. Parasitological, immunological, biochemical, and histopathological studies were applied as vaccine efficacy measures. The protective role of the tested vaccine was noted using the statistically marked reduction in brain cyst count, accompanied by remarkable levels of protective IFN-γ and antibodies, with amelioration of infection-induced oxidative stress and brain pathology. Ultimately, this experiment outlined the prospective role of a novel, natural, nano-encapsulated and mucosal vaccine adjuvant RA-SLNs as a propitious candidate against chronic toxoplasmosis.

T cell immunity ameliorates COVID-19 disease severity and provides post-exposure prophylaxis after peptide-vaccination, in Syrian hamsters.

The emergence of novel SARS-CoV-2 variants that resist neutralizing antibodies drew the attention to cellular immunity and calls for the development of alternative vaccination strategies to combat the pandemic. Here, we have assessed the kinetics of T cell responses and protective efficacy against severe COVID-19 in pre- and post-exposure settings, elicited by PolyPEPI-SCoV-2, a peptide based T cell vaccine. 75 Syrian hamsters were immunized subcutaneously with PolyPEPI-SCoV-2 on D0 and D14. On D42, hamsters were intranasally challenged with 102 TCID50 of the virus. To analyze immunogenicity by IFN-γ ELISPOT and antibody secretion, lymphoid tissues were collected both before (D0, D14, D28, D42) and after challenge (D44, D46, D49). To measure vaccine efficacy, lung tissue, throat swabs and nasal turbinate samples were assessed for viral load and histopathological changes. Further, body weight was monitored on D0, D28, D42 and every day after challenge. The vaccine induced robust activation of T cells against all SARS-CoV-2 structural proteins that were rapidly boosted after virus challenge compared to control animals (~4-fold, p<0.05). A single dose of PolyPEPI-SCoV-2 administered one day after challenge also resulted in elevated T cell response (p<0.01). The vaccination did not induce virus-specific antibodies and viral load reduction. Still, peptide vaccination significantly reduced body weight loss (p<0.001), relative lung weight (p<0.05) and lung lesions (p<0.05), in both settings. Our study provides first proof of concept data on the contribution of T cell immunity on disease course and provide rationale for the use of T cell-based peptide vaccines against both novel SARS-CoV-2 variants and supports post-exposure prophylaxis as alternative vaccination strategy against COVID-19.

Measurement of Vaccine Efficacy and Covid-19 Risk Probability

The effectiveness and efficacy of the Covid-19 vaccine are important indicators considered in implementing the vaccination program. This indicator is also a consideration for the community to receive the Covid-19 vaccine in the future. This calculation informs the community about the importance of the efficacy and effectiveness of the Covid-19 vaccination.

Relação entre Idade e Imunidade para a COVID-19 em Profissionais de Saúde

Introduction The initiation of vaccination against Covid-19 raises some questions about the effectiveness, safety, durability of protection and the need for booster doses. The measurement of anti-spike IgG antibodies can help to answer these questions, as well as to reduce the contagion between Health Professionals and patients, ensuring the responsiveness of the National Health Service. Objectives Assess the anti-spike IgG antibody titles in vaccinated healthcare professionals at three and six months after full vaccination and how they vary with age. Methodology Anti-spike IgG antibodies against SARS-CoV2 were measured in a group of 923 health professionals from a Local Health Unit at three and six months after vaccination with the COMIRNATY® vaccine. The serological test used was the fully automated chemiluminescent immunoassay (Abbott). Epidemiological data was collected, such as Age, Gender and Professional Category, and it was determined whether there was a relationship between antibody titles and age. Results Of the 923 participants, the majority were women (81.4%), and the mean age was 45.51 years. Antibody titles averaged 6452.61 AU/mL at three months and 2011.17AU/mL at six months, with a drop of 68.84% from three to six months. From the results obtained, it can be noted that antibody values vary with age: the older the age, the lower the number of antibodies produced, and from three to six months this association is stronger, that is, older people produce fewer antibodies, and they lose them intensely over time. Discussion/Conclusion The measurement of IgG anti-spike antibodies cannot be seen as a unique measure of vaccine efficacy, there is also an important component of humoral immunity that we still do not know for sure the true importance. Antibody dosing may provide relevant information about efficacy, the need for vaccine booster, identification of risk groups and contributing to disease prevention in Health Professionals. This study allows us to identify that most people responded well to vaccination, but that the antibodies drop sharply from three to six months. It also makes it possible to establish a relationship, albeit tenuous, between age and antibody titles, reinforcing the idea of boosting vaccination in older people. Keywords: Covid-19, Vaccine, Immunity, Antibodies, Age, Occupational Health.

Oral Cholera Vaccine Efficacy and Effectiveness.

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the “gold standard”, effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease.

Measuring Vaccine Efficacy Against Infection and Disease in Clinical Trials: Sources and Magnitude of Bias in Coronavirus Disease 2019 (COVID-19) Vaccine Efficacy Estimates.

BackgroundPhase III trials have estimated coronavirus disease 2019 (COVID-19) vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections.MethodsWe developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus, and imperfect sensitivity and specificity of tests for infection and antibodies. We estimated expected biases in VE against symptomatic, asymptomatic, and any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and against disease following infection for a range of vaccine characteristics and measurement approaches, and the likely overall biases for published trial results that included asymptomatic infections.ResultsVE against asymptomatic infection measured by polymerase chain reaction (PCR) or serology is expected to be low or negative for vaccines that prevent disease but not infection. VE against any infection is overestimated when asymptomatic infections are less likely to be detected than symptomatic infections and the vaccine protects against symptom development. A competing bias toward underestimation arises for estimates based on tests with imperfect specificity, especially when testing is performed frequently. Our model indicates considerable uncertainty in Oxford-AstraZeneca ChAdOx1 and Janssen Ad26.COV2.S VE against any infection, with slightly higher than published, bias-adjusted values of 59.0% (95% uncertainty interval [UI] 38.4–77.1) and 70.9% (95% UI 49.8–80.7), respectively.ConclusionsMultiple biases are likely to influence COVID-19 VE estimates, potentially explaining the observed difference between ChAdOx1 and Ad26.COV2.S vaccines. These biases should be considered when interpreting both efficacy and effectiveness study results.

Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term.

Dengue virus serotypes 1 to 4 (DENV1–4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies. Low dengue disease incidence after the recent Zika pandemic led to the hypothesis that ZIKV infection is also transiently cross protective. We investigated antibody kinetics in 4189 children up to 11 years after one and multiple DENV and ZIKV infections in longitudinal cohorts in Nicaragua. We used a DENV inhibition enzyme-linked immunosorbent assay (iELISA), which measures antibodies associated with protection against dengue and Zika disease and with enhancement of dengue disease severity. Unexpectedly, we found that overall DENV iELISA titers stabilized by 8 months after primary DENV infection to a half-life longer than a human life and waned, although gradually, after secondary DENV infection. Similarly, DENV iELISA titers were stable or rose after primary ZIKV infection but declined in individuals with histories of DENV and ZIKV infection. In contrast, kinetics of anti-ZIKV antibodies after ZIKV infection were similar regardless of prior DENV immunity. We observed heterogeneity in DENV iELISA titer, suggesting that individual antibody titer set point, rather than waning, is important for future dengue disease risk. Together, these findings change our understanding of anti-flavivirus antibody kinetics and have implications for measuring vaccine efficacy and for predicting future dengue and Zika outbreaks.

Estimating Vaccine Efficacy Against Transmission via Effect on Viral Load.

Determining policies to end the SARS-CoV-2 pandemic will require an understanding of the efficacy and effectiveness (hereafter, efficacy) of vaccines. Beyond the efficacy against severe disease and symptomatic and asymptomatic infection, understanding vaccine efficacy against virus transmission, including efficacy against transmission of different viral variants, will help model epidemic trajectory and determine appropriate control measures. Recent studies have proposed using random virologic testing in individual randomized controlled trials to improve estimation of vaccine efficacy against infection. We propose to further use the viral load measures from these tests to estimate efficacy against transmission. This estimation requires a model of the relationship between viral load and transmissibility and assumptions about the vaccine effect on transmission and the progress of the epidemic. We describe these key assumptions, potential violations of them, and solutions that can be implemented to mitigate these violations. Assessing these assumptions and implementing this random sampling, with viral load measures, will enable better estimation of the crucial measure of vaccine efficacy against transmission.

Is the Immunization of Pregnant Women against COVID-19 Justified?

Maternal immunization against some infectious diseases can offer significant advantages for women, preventing maternal morbidity and mortality, or for offspring, preventing fetal disease and conferring passive immunity to neonates. Recently, clinical trials specifically to evaluate the immunogenicity, safety, and tolerability of some of the available coronavirus disease 2019 (COVID-19) vaccines in pregnant and lactating women have been planned, initiated and, in some cases, completed. This paper discusses whether the immunization of pregnant women against COVID-19 is justified and presents knowledge about the immunogenicity and safety of mRNA COVID-19 vaccines for these subjects. The results of recent studies indicate that pregnant women are at increased risk of developing severe disease compared with nonpregnant women of the same age. Studies carried out with mRNA vaccines indicate that the immunogenicity, safety and tolerability of these preventive measures in pregnant women are not different from those in nonpregnant women of the same age. Moreover, antibodies are efficiently transferred through the placenta and can be detected in breastmilk, suggesting a potential prevention of infection in the child. All these findings authorize the use of mRNA vaccines in pregnant women to protect both the mother and the child. However, further studies with larger sample size and with follow-up of the pregnant women vaccinated during different periods of pregnancy and their children are needed to better characterize the immune response of pregnant women, to define when these vaccines should be administered to obtain the best protection, and to measure vaccine efficacy against virus variants in both mothers and infants. COVID-19 vaccines based on different technological platforms cannot presently be used, and their role in pregnant women should be clarified.

Defining Efficacy of Chikungunya Virus Candidate Vaccines: Different Endpoints Derived From the Virus—Cytokine—Ferritin (VCF) Model

Following the disruptive epidemics throughout the Indian Ocean, Southeast Asia and the Americas, efforts have been deployed to develop an effective vaccine against chikungunya virus (CHIKV). The continuous threat of CHIKV (re-)emergence and the huge public health and economic impact of the epidemics, makes the development of a safe and effective vaccine a priority. Several platforms have been used to develop candidate vaccines, but there is no consensus about how to translate results from preclinical models to predict efficacy in humans. This paper outlines a concept of what constitutes an effective vaccine against CHIKV, which may be applied to other viral vaccines as well. Defining endpoints for an effective vaccine is dependent on a proper understanding of the pathogenesis and immune response triggered during infection. The preclinical model adopted to evaluate experimental vaccines is imperative for the translation of preclinical efficacy data to humans. Several CHIKV animal models exist; however, not all provide suitable endpoints for measuring vaccine efficacy. This review summarizes the current knowledge related to CHIKV pathogenesis and the correlates of protection. We then define what would constitute an effective CHIKV vaccine in humans using four key endpoints, namely: (i) prevention of chronic disease, (ii) prevention of acute disease, (iii) prevention of transmission to mosquitoes, and (iv) complete prevention of infection. Lastly, we address some of the gaps that prevent translation of immunogenicity and efficacy findings from preclinical models to humans, and we propose to use the combination of virus–cytokine–ferritin levels as a read-out for measuring vaccine-induced protection.

Population (Antibody) Testing for COVID-19-Technical Challenges, Application and Relevance, an English Perspective.

In the UK, population virus or antibody testing using virus swabs, serum samples, blood spots or oral fluids has been performed to a limited extent for several diseases including measles, mumps, rubella and hepatitis and HIV. The collection of population-based infection and immunity data is key to the monitoring of disease prevalence and assessing the effectiveness of interventions such as behavioural modifications and vaccination. In particular, the biological properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its interaction with the human host have presented several challenges towards the development of population-based immunity testing. Measuring SARS-CoV-2 immunity requires the development of antibody assays of acceptable sensitivity and specificity which are capable of accurately detecting seroprevalence and differentiating protection from non-protective responses. Now that anti-COVID-19 vaccines are becoming available there is a pressing need to measure vaccine efficacy and the development of herd immunity. The unprecedented impact of the SARS-CoV-2 pandemic in the UK in terms of morbidity, mortality, and economic and social disruption has mobilized a national scientific effort to learn more about this virus. In this article, the challenges of testing for SARS-CoV-2 infection, particularly in relation to population-based immunity testing, will be considered and examples given of relevant national level studies.

Correlates of Vaccine-Induced Protection against SARS-CoV-2.

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

Fleece rot and dermatophilosis (lumpy wool) in sheep: opportunities and challenges for new vaccines

During prolonged wetting of the fleece, proliferation of bacterial flora often dominated by Pseudomonas aeruginosa or Dermatophilus congolensis can induce dermatitis and fleece damage termed fleece rot and dermatophilosis respectively, which predispose sheep to blowfly strike. A large research effort in the 1980s and 1990s on vaccines to control fleece rot and dermatophilosis met with limited success. This review examines theoretical and technological advances in microbial ecology, pathogenesis, immunology, vaccine development and the characterisation of microbial virulence factors that create new opportunities for development of vaccines against these diseases. Genomic technologies have now created new opportunities for examining microbial dynamics and pathogen virulence in dermatitis. An effective vaccine requires the combination of appropriate antigens with an adjuvant that elicits a protective immune response that ideally provides long-lasting protection in the field. A clinical goal informed by epidemiological, economic and animal welfare values is needed as a measure of vaccine efficacy. Due to dependence of fleece rot and dermatophilosis on sporadic wet conditions for their expression, vaccine development would be expedited by in vitro correlates of immune protection. The efficacy of vaccines is influenced by genetic and phenotypic characteristics of the animal. Advances in understanding vaccine responsiveness, immune defence in skin and immune competence in sheep should also inform any renewed efforts to develop new fleece rot and dermatophilosis vaccines. The commercial imperatives for new vaccines are likely to continue to increase as the animal welfare expectations of society intensify and reliance on pharmacotherapeutics decrease due to chemical resistance, market pressures and societal influences. Vaccines should be considered part of an integrated disease control strategy, in combination with genetic selection for general immune competence and resistance to specific diseases, as well as management practices that minimise stress and opportunities for disease transmission. The strategy could help preserve the efficacy of pharmacotherapeutics as tactical interventions to alleviate compromised welfare when adverse environmental conditions lead to a break down in integrated strategic disease control. P. aeruginosa and D. congolensis are formidable pathogens and development of effective vaccines remains a substantial challenge.

Immune correlates analysis using vaccinees from test negative designs.

Determining the effect of vaccine-induced immune response on disease risk is an important goal of vaccinology. Typically, immune correlates analyses are conducted prospectively with immune response measured shortly after vaccination and subsequent disease status regressed on immune response. In outbreaks and rare disease settings, collecting samples from all vaccinees is not feasible. The test negative design is a retrospective design used to measure vaccine efficacy where symptomatic individuals who present at a clinic are assessed for relevant disease (cases) or some other disease (controls) and vaccination status ascertained. This article proposes that test negative vaccinees have immune response to vaccine assessed both for relevant (e.g., Ebola) and irrelevant (e.g., vector) proteins. If the latter immune response is unaffected by active (Ebola) infection, and is correlated with the relevant immune response, it can serve as a proxy for the immune response of interest proximal to infection. We show that logistic regression using imputed immune response as the covariate and case disease as outcome can estimate the prospective immune response slope and detail the assumptions needed for unbiased inference. The method is evaluated by simulation under various scenarios including constant and decaying immune response. A simulated dataset motivated by ring vaccination for an ongoing Ebola outbreak is analyzed.

CoV-AbDab: the coronavirus antibody database.

MotivationThe emergence of a novel strain of betacoronavirus, SARS-CoV-2, has led to a pandemic that has been associated with over 700,000 deaths as of 5th August 2020. Research is ongoing around the world to create vaccines and therapies to minimise rates of disease spread and mortality. Crucial to these efforts are molecular characterisations of neutralising antibodies to SARS-CoV-2. Such antibodies would be valuable for measuring vaccine efficacy, diagnosing exposure, and developing effective biotherapeutics. Here, we describe our new database, CoV-AbDab, which already contains data on over 1400 published/patented antibodies and nanobodies known to bind to at least one betacoronavirus. This database is the first consolidation of antibodies known to bind SARS-CoV-2 as well as other betacoronaviruses such as SARS-CoV-1 and MERS-CoV. It contains relevant metadata including evidence of cross-neutralisation, antibody/nanobody origin, full variable domain sequence (where available) and germline assignments, epitope region, links to relevant PDB entries, homology models, and source literature.ResultsOn 5th August 2020, CoV-AbDab referenced sequence information on 1402 anti-coronavirus antibodies and nanobodies, spanning 66 papers and 21 patents. Of these, 1131 bind to SARS-CoV-2.AvailabilityCoV-AbDab is free to access and download without registration at http://opig.stats.ox.ac.uk/webapps/coronavirus. Community submissions are encouraged.Supplementary informationbtaa739_Supplementary_DataClick here for additional data file.Supplementary data are available at Bioinformatics online.

A Review of Vaccine Efficacy Measures

To fully understand the assessments of vaccine efficacy and safety, the crucial information needed for regulatory approval, one must understand the principles of vaccine epidemiology. In this review article, we go through some of the key concepts in vaccine epidemiology