The current study experimentally investigates the differences in data quality between a face-to-face and a web survey. Based on satisficing theory, it was hypothesized that web survey respondents ...would be more likely to satisfice for a multitude of reasons, thereby producing data of lower quality. The data show support for the hypothesis. Web survey respondents were shown to produce a higher "don't know" response rate, to differentiate less on rating scales, and to produce more item nonresponse than face-to-face survey respondents.
Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19 Stephenson, Kathryn E; Le Gars, Mathieu; Sadoff, Jerald ...
JAMA : the journal of the American Medical Association,
04/2021, Letnik:
325, Številka:
15
Journal Article
Recenzirano
Odprti dostop
IMPORTANCE: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. OBJECTIVE: To evaluate the immunogenicity of the Ad26.COV2.S vaccine ...(Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. INTERVENTIONS: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). MAIN OUTCOMES AND MEASURES: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. RESULTS: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. CONCLUSION AND RELEVANCE: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04436276
Replication-incompetent adenoviral vectors have been under investigation as a platform to carry a variety of transgenes, and express them as a basis for vaccine development. A replication-incompetent ...adenoviral vector based on human adenovirus type 26 (Ad26) has been evaluated in several clinical trials.
The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and features of recombinant viral vector vaccines. This paper reviews features of the Ad26 vectors, including tabulation of safety and risk assessment characteristics of Ad26-based vaccines.
In the Ad26 vector, deletion of E1 gene rendering the vector replication incompetent is combined with additional genetic engineering for vaccine manufacturability and transgene expression optimization. These vaccines can be manufactured in mammalian cell lines at scale providing an effective, flexible system for high-yield manufacturing. Ad26 vector vaccines have favorable thermostability profiles, compatible with vaccine supply chains.
Safety data are compiled in the Ad26 vaccine safety database version 4.0, with unblinded data from 23 ongoing and completed clinical studies for 3912 participants in five different Ad26-based vaccine programs. Overall, Ad26-based vaccines have been well tolerated, with no significant safety issues identified. Evaluation of Ad26-based vaccines is continuing, with >114,000 participants vaccinated as of 4th September 2020.
Extensive evaluation of immunogenicity in humans shows strong, durable humoral and cellular immune responses. Clinical trials have not revealed impact of pre-existing immunity to Ad26 on vaccine immunogenicity, even in the presence of Ad26 neutralizing antibody titers or Ad26-targeting T cell responses at baseline.
The first Ad26-based vaccine, against Ebola virus, received marketing authorization from EC on 1st July 2020, as part of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen. New developments based on Ad26 vectors are underway, including a COVID-19 vaccine, which is currently in phase 3 of clinical evaluation.
Effects of personalizing survey invitations on response rates have been extensively researched in the realm of mail surveys. Commonly, it is found that response rates increase when personalization is ...applied. Recently, efforts have been made to investigate whether these findings extend to the field of Web surveys that use e-mail invitations. Using data from a Web experiment conducted among first-year university students, personalization of e-mail invitations is shown to have significantly increased the response rate by 7.8 percentage points. From the theory that personalization decreases the level of anonymity and perceived privacy, differences in responses to sensitive questions were expected. However, no effects of personalization on the responses to a question probing for respondents’ sexual behavior were found.
Inspired by the positive effects of incentives on mail survey response rates, researchers have started using incentives to increase response rates to Web surveys. The established best practice of ...presending cash incentives is difficult to implement in Web surveys, and studies suggest that its presumed effects might not be witnessed in Web surveys. In contrast, several studies have found that lotteries can significantly increase Web survey response rates. Some authors have argued that this could reflect the fact that Internet users have come to expect Web surveys to be associated with lotteries. An experimental study among university students found that the lottery influences the Web survey response rates, but there are indications that different subgroups might be more influenced by this incentive than others. The observed differences are interpreted along the lines of possible differences in the degree to which different respondent groups expect incentives in return for their participation.
•Homologous and heterologous Ad26.COV2.S boosters elicited neutralizing antibodies.•Responses were durable against SARS-CoV-2 reference strain and variants of concern.•Ad26 pre-existing immunity does ...not impact vaccine-elicited immune responses.
COVID-19 vaccine boosters may optimize durability of protection against variants of concern (VOCs). In this randomized, double-blind, phase 2 trial, participants received 3 different dose levels of an Ad26.COV2.S booster (5 × 1010 vp viral particles, 2.5 × 1010 vp, or 1 × 1010 vp) ≥6 months post–primary vaccination with either single-dose Ad26.COV2.S (homologous boost; n = 774) or 2-dose BNT162b2 (heterologous boost; n = 758). Primary endpoints were noninferiority of neutralizing antibody responses at Day 15 post-boost versus Day 29 post–primary vaccination. Secondary endpoints included reactogenicity/safety and neutralizing antibody responses to VOCs. All primary endpoints passed prespecified hierarchical noninferiority criteria by Day 15 post-boost. Geometric mean increases in neutralizing antibody titers against the D614G reference strain ranged from 5.5 to 6.8 at Day 15 for homologous boosting and 12.6 to 22.0 for heterologous boosting. For VOCs, heterologous boosting elicited higher neutralizing antibody responses than homologous boosting. Neutralizing antibody responses were dose-dependent and durable for ≥6 months post-boost. More solicited systemic adverse events occurred following heterologous versus homologous boosting.
Trial Registration:ClinicalTrials.gov Identifier: NCT04999111.
Background
The Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS) was developed to assess the severity of respiratory syncytial virus (RSV) infection in ...children. Because young children cannot report how they feel or function, ratings are based on observations by the child's caregiver (Observer‐Reported Outcome questionnaire ObsRO) and clinician (Clinician‐Reported Outcome questionnaire ClinRO). This prospective study aimed to evaluate the psychometric properties of the PRESORS.
Methods
The PRESORS version 6 ObsRO and ClinRO were evaluated in children with RSV infection requiring hospitalization in centers in the United States, Argentina, and Chile. Assessments were performed from days 1 to 7 by the child's caregiver and clinician. To assess inter‐rater reliability, two clinicians independently performed the ClinRO near in time.
Results
A total of 124 children aged ≤36 months were enrolled (mean age, 8 months). Factor analysis demonstrated that RSV severity consists of two dimensions, respiratory signs and illness behavior, and that these dimensions were consistent over time. The inter‐rater reliability for the ClinRO was 0.66 (95% confidence interval CI, 0.55–0.75) but improved to 0.79 (95% CI, 0.71–0.86) after removing one outlying site, suggesting that quantifying RSV severity is not trivial, even using qualified raters, but that an adequate inter‐rater reliability is achievable with the PRESORS through adequate training. ClinRO and ObsRO displayed acceptable internal consistency and acceptable convergent validity with the Respiratory Syncytial Virus Network Scale, global impression scores, and key hospital characteristics.
Conclusions
The PRESORS is relevant and appropriate for assessing the severity of RSV infection in infants requiring hospitalization.
Abstract
This secondary analysis of the phase 3 ENSEMBLE trial (NCT04505722) assessed the impact of preexisting humoral immunity to adenovirus 26 (Ad26) on the immunogenicity of Ad26.COV2.S-elicited ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibody levels in 380 participants in Brazil, South Africa, and the United States. Among those vaccinated in Brazil and South Africa, 31% and 66%, respectively, had prevaccination serum-neutralizing activity against Ad26, with little preexisting immunity detected in the United States. Vaccine recipients in each country had similar postvaccination spike (S) protein–binding antibody levels, indicating that baseline immunity to Ad26 has no clear impact on vaccine-induced immune responses.
Adenovirus 26 (Ad26)–based vaccines have been evaluated in multiple clinical vaccine programs, including for coronavirus disease 2019 (COVID-19). This study assessed the potential impact of preexisting humoral immunity against Ad26 on humoral immunogenicity of the COVID-19 vaccine Ad26.COV2.S.
This study investigates the link between the effort undertaken to collect survey data and the nonresponse error on a key survey estimate. For this purpose a threefold analysis was conducted. First, ...the level of nonresponse error and its composition is charted. Second, it is investigated whether these levels change throughout the fieldwork period. This helps answering the question whether collecting more data implies higher data quality. This type of analysis also provides a possible framework for a dynamic process control during the fieldwork period. A third and final analysis links interviewer efforts (in terms of number of contact attempts) to nonresponse error and its composition. The results show that error due to noncontact is 2.6 times higher than error due to refusal, even though the refusal rate is almost two times higher than the noncontact rate. Also, the results suggest that collecting more data does not necessarily imply higher data quality and that a higher number of contact attempts does not markedly reduce the nonresponse error in absolute terms. The analysis uncovers the underlying process responsible for this latter finding.
•One dose of Ad26.COV2.S elicited high neutralizing and binding antibody levels.•Antibody levels persisted through 8 months (neutralizing) and 6 months (binding).•A homologous 6-month booster led to ...a rapid and robust increase in antibody titers.•Ad26.COV2.S elicited immune memory supporting anamnestic responses after boosting.•Ad26.COV2.S may provide sustained efficacy against reference and variant strains.
Ad26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.
In randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 1010 viral particles vp) followed by booster doses of 5 × 1010 vp or 1.25 × 1010 vp. Neutralizing antibody levels were determined by a virus neutralization assay (VNA) approximately 8–9 months after dose 1. Binding and neutralizing antibody levels were evaluated by an enzyme-linked immunosorbent assay and pseudotyped VNA 6 months after dose 1 and 7 and 28 days after boosting.
Data were analyzed from phase 1/2a participants enrolled from 22 July–18 December 2020 (Cohort 1a, 18–55 years y, N = 25; Cohort 2a, 18–55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18–55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8–9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 1010 vp 2-month booster dose increased binding antibodies by 4.9- to 6.2-fold 14 days post-boost versus 28 days after initial immunization. A 6-month booster elicited a steep and robust 9-fold increase in binding antibody levels 7 days post-boost. A 5.0-fold increase in neutralizing antibodies was observed by 28 days post-boost for the Beta variant. A 1.25 × 1010 vp 6-month booster elicited a 3.6-fold increase in binding antibody levels at 7 days post-boost versus pre-boost, with a similar magnitude of post-boost responses in both age groups.
Single-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.
Trial Registration:ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.
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