Strategic Advisory Group Of Experts Research Articles

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation, an open label, phase IV, randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.

Determination of COVID-19 Vaccine Hesitancy Among University Students.

IntroductionWith the sudden outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), vaccines appear to be the most efficient measure in combating spread. However, vaccines are only effective if a community collectively uptakes vaccination. This approach is growing increasingly difficult with the emergence of ‘Vaccine Hesitancy.’ This paper aims to determine the association between university curricula and the degree of hesitancy for the COVID-19 vaccine.MethodsThe online questionnaire assessed demographic data, prior knowledge of vaccines, attitude towards COVID-19 vaccines using an adapted version of the WHO Strategic Advisory Group of Experts (SAGE) Working Group’s Vaccine Hesitancy Survey (VHS) and factors likely to motivate vaccine uptake. By using binary scoring, the degree of hesitancy among students was determined. Exploratory Factor Analysis (EFA) on VHS revealed underlying causes of hesitancy. To analyze the dependence between hesitancy and curriculum, a chi-squared test was conducted.ResultsMedical students scored higher for prior knowledge of vaccines (M = 3.54) as opposed to non-medical students (M = 3.49). Medical students responded favorably to COVID-19 vaccines with only 1.37% showing hesitancy for all nine items of VHS, compared to 2.55% of non-medical students. EFA produced three subscales within the VHS: lack of confidence, risk factor concern, and misinformation. The lack of confidence factor accounted for 65% of the data obtained. The chi-square test solidified that vaccine hesitancy is dependent on curriculum.ConclusionThe majority of non-medical students showed hesitancy towards obtaining COVID-19 vaccines compared to medical students who were more willing, largely owing to their knowledge and understanding of vaccines.

Using participatory action research to improve immunization utilization in areas with pockets of unimmunized children in Nigeria

BackgroundIn 2005, Nigeria adopted the Reaching Every Ward strategy to improve vaccination coverage for children 0–23 months of age. By 2015, Ogun state had full coverage (100%) in 12 of its 20 local government areas, but eight had pockets of unimmunized children, with the highest burden (37%) in Remo North. A participatory action research (PAR) approach was used to facilitate implementation of local solutions to contextual barriers to immunization in Remo North. This article assesses and seeks to explain the outcomes of the PAR implemented in Remo North to understand whether and possibly how it improved immunization utilization.MethodsThe PAR intervention took place from 2016 to 2017. It involved two (4-month) cycles of dialogue and action between community members, frontline health workers and local government officials in two wards of Remo North, facilitated by the research team. The PAR was assessed using a pre/post-intervention-only design with mixed methods. These included household surveys of caregivers of 215 and 213 children, respectively, 25 semi-structured interviews with stakeholders involved in immunization service delivery and 16 focus group discussions with community members. Data were analysed using the Strategic Advisory Group of Experts (SAGE) vaccine hesitancy framework.ResultsCollaboration among the three stakeholder groups enabled the development and implementation of solutions to identified problems related to access to and use of immunization services. At endline, assessment by card for children older than 9 months revealed a significant increase in those fully immunized, from 60.7% at baseline to 90.9% (p < .05). A significantly greater number of caregivers visited fixed government health facilities for routine immunization at endline (83.2%) than at baseline (54.2%) (p < .05). The reasons reported by caregivers for improved utilization of routine immunization services were increased community mobilization activities and improved responsiveness of the health workers. Spillover effects into maternal health services enhanced the use of immunization services by caregivers. Spontaneous scale-up of actions occurred across Remo North due to the involvement of local government officials.ConclusionThe PAR approach achieved contextual solutions to problems identified by communities. Collection and integration of evidence into discussions/dialogues with stakeholders can lead to change. Leveraging existing structures and resources enhanced effectiveness.

Equitable and Feasible Distribution of SARS-CoV-2 Vaccines for All in Africa.

ABSTRACT.As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative’s campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization’s Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations’ populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

Barriers and facilitators to influenza and pneumococcal vaccine hesitancy in rheumatoid arthritis: a qualitative study

Immunization is an essential component of rheumatoid arthritis (RA) care. Nevertheless, vaccine coverage in RA is suboptimal. Contextual, individual, and vaccine-related factors influence vaccine acceptance. However, barriers and facilitators of vaccination in RA are not well defined. The aim of this study was to assess perspectives of RA patients and health care professionals (HCPs) involved in RA care of barriers and facilitators regarding influenza and pneumococcal vaccines. Eight focus groups (4 with RA patients and 4 with HCPs), and eight semi-structured open-ended individual interviews with vaccine hesitant RA patients were conducted. Data were audio-recorded, transcribed verbatim, and imported to the MAXQDA software. Analysis using the framework of vaccine hesitancy proposed by the Strategic Advisory Group of Experts (SAGE) on Immunization was conducted. RA patients and HCPs reported common and specific barriers and facilitators to influenza vaccination that included contextual, individual and/or group, and vaccine and/or vaccination specific factors. A key contextual influence on vaccination was patients' perception of the media, pharmaceutical industry, authorities, scientists, and the medical community at large. Among the individual-related influences, experiences with vaccination, knowledge/awareness, and beliefs about health and disease prevention were considered to impact vaccine-acceptance. Vaccine-related factors including concerns of vaccine side effects such as RA flares, safety of new formulations, mechanism of action, access to vaccines and costs associated with vaccination were identified as actionable barriers. Acknowledging RA patients' perceived barriers to influenza and pneumococcal vaccination and implementing specific strategies to address them might increase vaccination coverage in this population.

Estimating the Impact of Vaccination on Antimicrobial-Resistant Typhoid Fever in Gavi-73 Countries

Background: Multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The recent development and licensure of typhoid conjugate vaccines (TCVs) provide an opportunity to limit the transmission and burden of antimicrobial-resistant (AMR) typhoid fever. Methods: We combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance to predict the burden of AMR typhoid fever across Gavi-73 countries. We considered FQNS and MDR separately. The impact of vaccination was predicted based on forecasts of vaccine coverage. We explored how the potential impact of vaccination on the proportion of cases that were AMR varied depending on key model parameters. Findings: The introduction of routine immunization with TCV at 9 months of age with a catch-up campaign to 15 years of age was predicted to avert 46-74% of all typhoid fever cases in Gavi-73 countries. Vaccination was predicted to reduce the relative prevalence of AMR typhoid fever by 16% (95% prediction interval (PI): 0-49%). TCV introduction with a catch-up campaign was predicted to avert 42.5 million (95% PI: 24.8-62.8 million) cases and 506,000 (95% PI: 187,000-1.9 million) deaths due to FQNS typhoid fever and 21.2 million (95% PI: 16.4-26.5 million) cases and 342,000 (95% PI: 135,000-1.5 million) deaths from MDR typhoid fever over 10 years following introduction. Interpretation: Our results indicate the benefits of prioritizing TCV introduction for countries with a high avertable burden of FQNS and MDR typhoid fever. Funding: The Bill & Melinda Gates Foundation. Declaration of Interest: AJP chairs the UK Department of Health’s (DoH) Joint Committee on Vaccination and Immunisation (JCVI) and and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts. VEP has received reimbursement from Merck and Pfizer for travel expenses to Scientific Input Engagements unrelated to the subject of this manuscript and is a member of the World Health Organization’s (WHO) Immunization and Vaccine-related Implementation Research Advisory Committee. The views expressed in this manuscript are those of the authors and do not necessarily reflect the views of the JCVI, the DoH, or the WHO.

Assessing vaccine introduction and uptake timelines in Gavi-supported countries: are introduction timelines accelerating across vaccine delivery platforms?

BackgroundPrevious studies identified factors influencing regulatory approval to introduction timelines for individual vaccines. However, introduction and uptake timelines have not been comprehensively assessed across the portfolio of Gavi-supported vaccines.MethodsWe analysed...

Vaccine Hesitancy: COVID-19 and Influenza Vaccine Willingness among Parents in Wuxi, China-A Cross-Sectional Study.

Objectives: We aimed to (1) assess parental hesitancy about category A (Expanded Program on Immunization (EPI)) and B (non-EPI) vaccines, (2) assess parental willingness for COVID-19 and influenza vaccinations, and (3) explore the association of vaccination hesitancy of parents and healthcare workers (HCWs). Methods: The study was performed in Wuxi, eastern China between 21 September 2020 and 17 October 2020. Parents of children aged <18 years and HCWs were recruited from the selected immunization clinics. Vaccine hesitancy was assessed using the Strategic Advisory Group of Experts (SAGE) vaccine hesitancy survey (VHS) by summing the total score for 10 items (maximum 50 points). Results: A total of 3009 parents and 86 HCWs were included in the analysis. The category A VHS scores were significantly higher than the category B VHS scores (p = 0.000). Overall, 59.3% and 52.4% of parents reported willingness to avail COVID-19 and influenza vaccination for their children, respectively; 51.2% of the HCWs wanted to be vaccinated against COVID-19. Parental category B VHS scores were associated with HCW category B VHS scores (r = 0.928, p = 0.008). Conclusions: In China, parents are more hesitant about category B vaccines than category A vaccines. More than 40% of parents showed hesitancy and a refusal to use COVID-19 and influenza vaccines.

Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster

Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster

National Immunization Technical Advisory Groups (NITAGs): A schema for evaluating and comparing foundation instruments and NITAG operations

The individual and community health benefits of vaccination have received significant attention and are now well understood. However, much less is known about immunization as a regulated space, its principles and standards and its institutions and instruments. In 2011, the World Health Organization (WHO) recommended that National Immunization Technical Advisory Groups (NITAGs) be established in each member country. NITAGSs are envisioned as independent, multidisciplinary expert groups within the national immunization framework, tasked with providing evidence-based evaluations and recommendations to governmental decision-makers about specific vaccines, vaccine-dosing, vaccine program development and immunization policy and practice more generally. As of 2020, 171 WHO countries have formed NITAGs. The widespread formation of NITAGs has highlighted an absence of sustained scholarship around immunization as a policy area subject to law, and it has given rise to many governance and operational questions. In 2017, for example, representatives of the Global NITAG Network (GNN) agreed that there is insufficient understanding of the impact of law on the functioning of NITAGs. Similarly, the Strategic Advisory Group of Experts on Immunization called for research into the variety of ways in which legislation and regulation have been used to promote immunization at a national level and to achieve different ends in relation to immunization and NITAG functioning. In answer to this call, the NITAG Environmental Scan (Project) was initiated. Drawing on scholarship around good governance, this article offers a comprehensive common assessment schema for critically and systematically approaching questions about NITAG governance and operation, applying that schema to the foundation instrument of the Côte d’Ivoire’s NITAG. It also reports on how well the schema is engaged by the NITAG foundation instruments in other GNN countries.

Assessment of Vaccine Hesitancy to a COVID-19 Vaccine in Cameroonian Adults and Its Global Implication.

Since the outbreak of COVID-19 in December 2019, no global consensus treatment has been developed and generally accepted for the disease. However, eradicating the disease will require a safe and efficacious vaccine. In order to prepare for the eventual development of a safe and efficacious COVID-19 vaccine and to enhance its uptake, it is imperative to assess vaccine hesitancy in Cameroonians. After obtaining ethical clearance from the Institutional Review Board of the University of Buea, a questionnaire was administered (May–August 2020) to consenting adults either online or in person. A qualitative thematic analysis was done to analyze the participants’ answers to the open questions. A deductive approach was used, that is, the codes and patterns according to the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) Working Group Matrix of Determinants of vaccine hesitancy. The number of consenting adult Cameroonians who completed the questionnaire were 2512 (Two thousand five hundred and twelve). Vaccine hesitancy to a COVID-19 vaccine was 84.6% in Cameroonians. Using the WHO recommended Matrix of Determinant of Vaccine hesitancy, the most prominent determinants observed in this study were: Communication and Media Environment, Perception of pharmaceutical industry, Reliability and/or source of vaccine and cost. Most Cameroonians agree that even though there are benefits of a clinical trial, they will prefer it should be done out of the continent and involving African scientists for eventual acceptance and uptake. The concerns of safety, efficacy and confidence has to be addressed using a Public Engagement approach if a COVID-19 vaccine has to be administered successfully in Africa or Cameroon specifically. Since this study was carried out following WHO standards, its result can be compared to those of other studies carried out in different cultural settings using similar standards.

Trends in classifying vaccine hesitancy reasons reported in the WHO/UNICEF Joint Reporting Form, 2014–2017: Use and comparability of the Vaccine Hesitancy Matrix

ABSTRACT Since 2014, the World Health Organization (WHO) member states have been annually reporting vaccine hesitancy reasons, using the WHO/UNICEF Joint Reporting Form (JRF). The Vaccine Hesitancy Matrix (VHM), developed by a WHO strategic advisory group of experts, can serve as an important tool to categorize vaccine hesitancy reasons reported in the JRF. We aimed to describe the reasons for vaccine hesitancy reported globally from 2014 to 2017 to ascertain trends over time and understand the comparability of using the VHM to classify hesitancy reasons from 2014 to 2016 based on previously published literature. We conducted a quantitative content analysis to code and categorize vaccine hesitancy reasons reported in the JRF from 2014 to 2017. Vaccine hesitancy trends were consistent from 2014 to 2017, where vaccine hesitancy reasons were mainly related to “individual and group level influences” (59%) followed by “contextual influences” (25%), and “vaccine- or vaccination-specific issues” (16%). Comparability of our approach to categorize vaccine hesitancy to the previously published JRF data showed that results were mostly but not entirely consistent. Major differences in categorizing vaccine hesitancy were noted between two specific reasons – “experience with past vaccination” (under “individual and group influences”) and “risk/benefit- scientific evidence” (under “vaccine and vaccination-specific issues”); this was usually due to lack of clear definitions in some sub-categories and generic responses reported in the JRF. The JRF hesitancy module may benefit from modifications to improve the data quality. Understanding global vaccine hesitancy is crucial and JRF can serve as an important tool, especially with the potential introduction of a COVID-19 vaccine.

Measles Outbreak in the Philippines: Epidemiological and Clinical Characteristics of Hospitalized Children, 2016-2019

Background: Measles outbreaks increased worldwide during 2017-19. The largest outbreak in the World Health Organisation Western Pacific region occurred in the Philippines. The aim of this study was to summarise paediatric measles admissions to the national infectious diseases referral hospital in Manila during 2016 to 2019, and consider implications for the Philippines and the wider region. Methods: A retrospective single-centre observational study including 5,562 children aged under five years admitted with measles from January 2016 to December, 2019. We summarised sociodemographic and clinical characteristics, vaccine status, reported exposures and outcomes. Univariable and multivariable logistic regression analyses were undertaken to assess associations between different characteristics of hospitalised children and death. Findings: The median age of children hospitalised with measles was 11 months (interquartile range: 7-28). 84.5% of cases were reported not to have received any measles-containing vaccination (MCV). The case fatality rate was 3.2%, with 30% of deaths occurring among children aged less than 9 months. The following characteristics were associated with increased odds of death: admission during the period of the epidemic (adjusted odds ratio [AOR] 9.40, 95% CI 1.80-49.05), pneumonia (AOR 2.42, 95% CI 1.55-3.78), gastroenteritis (AOR 4.01, 95% CI 2.19-7.35), not receiving vitamin A supplementation (AOR 1.82, 95% CI 1.22-2.72), and not being vaccinated (AOR 2.09, 95% CI 1.07-4.07). Interpretation: No children died who had received two MCVs. MCV1 coverage in the Philippines declined to 72% in 2020. Routine immunization needs to be strengthened and earlier timing of MCV1 requires further evaluation to prevent further outbreaks. Funding Information: This work is in part funded by Nagasaki University (salary support for CS, KA, RN, KA, JS). Declaration of Interests: KM is a member of the WHO Strategic Advisory Group of Experts (SAGE) on Immunization. The other authors declare no conflicting interests Ethics Approval Statement: The study was approved by the SLH research ethics and review unit (Ref: SLH-RERU-2020-010-E Ver 2) and the School of Tropical Medicine and Global Health, Nagasaki University ethical committee (Ref: NU_TMGH_2020-106-0). This was a retrospective analysis of routinely collected anonymised data thus patient or caregiver consent was not required.

Tolerability and Immunogenicity After a Late Second Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222)

Background: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between first and second dose extends. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose, the immunity after an extended interval between the first and second dose of ChAdOx1 nCoV-19(AZD1222), and the response to a third dose as a late booster. Methods: Volunteers aged 18-55 years who were enrolled in a Phase 1/2 or Phase 2/3 clinical trial of ChAdOx1 nCoV-19 and had received either a single dose or two doses of 5×10 10 viral particles were invited back for vaccination. Reactogenicity and immunogenicity of a delayed second dose or a third dose are reported here.Findings: Antibody titres after a single dose and measured on d362 remain higher than the titres measured on d0 (62.61 EU; 95% CI 47.43-82.64 vs 1 EU 95% CI 1-16). 30 participants received a late second dose of ChAdOx1 nCoV-19 (median 44 weeks after first dose), antibody titres were higher in those with a longer interval between first and second dose (median EU for 8-12, 15-25, and 44-46 weeks were 923 [IQR 525-1764], 1860 [IQR 917-4934] and 3738 [IQR 1824-6625] respectively). 90 participants received a third dose and antibody titres were significantly higher following a third dose (FRNT50 612 [IQR 351-920]) when compared with the response 28 days after a second dose (FRNT 50 319 [IQR 176-591]. T-cell responses were also boosted after a third dose. Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose.Interpretation: A longer delay before the second dose of ChAdOx1 nCoV-19 leads to an increased antibody titre after the second dose. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.Funding: UK Research and Innovation (MC_PC_19055), Engineering and Physical Sciences Research Council (EP/R013756/1), National Institute for Health Research (COV19 OxfordVacc-01), Coalition for Epidemic Preparedness Innovations (Outbreak Response To Novel Coronavirus (COVID-19)), National Institute for Health Research Oxford Biomedical Research Centre (BRC4 Vaccines Theme), Thames Valley and South Midland’s NIHR Clinical Research Network, and AstraZeneca. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care.Declaration of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. SCG and AVSH are cofounders of and shareholders in Vaccitech (collaborators in the early development of this vaccine candidate) and named as inventors on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine (SCG only). TL is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and was a consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP is a NIHR Senior Investigator.Ethical Approval: In the UK, the COV001 and COV002 studies were approved by the South Central Berkshire Research Ethics Committee (COV001 reference 20/SC/0145, March 23, 2020; and COV002 reference 20/SC/0179; conditional approval April 8, full approval April 19, 2020).

Efficacy of ChAdOx1 nCoV-19&amp;nbsp;(AZD1222)&amp;nbsp;Vaccine Against SARS-CoV-2 VOC&amp;nbsp;202012/01&amp;nbsp;(B.1.1.7)

Background: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19infection in the United Kingdom from November 2020 with a transmission advantage over the previous variants of the virus. Here we report efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19, against this variant in comparison with non-B.1.1.7 lineages.Methods: Volunteers enrolled in phase II/III vaccine efficacy studies in the United Kingdom and randomised 1:1 to receive ChAdOx1 nCoV-19 or a MenACWY control vaccine, providedupper airway swabs every week during the trial and also if they developed possible symptomatic COVID-19 infection. Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2, and positive samples were sequenced through the COVID-19Genomics UK consortium (COG UK). NAAT data were used to assess the duration ofdetectable viral RNA in diagnostic specimens and the viral load. Anti-spike IgG wasmeasured by ELISA at baseline, 14 and 28 days after prime and 28 days after boostervaccination. Neutralising antibody responses were measured using a live virus neutralisation assay against the B.1.1.7 and Victoria lineages of the virus. The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cut-off on Jan 14, 2021. Vaccine efficacy was calculated as 1 − relative risk derived from a robust Poisson regression model. This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137.5Findings: Between 1st October 2020 and 14th January 2021, 499 participants developed Covid-19infection. 1524 NAAT positive nose/throat swabs were collected from these participants during the trial. Of these, 323 swabs from 256 participants were successfully sequenced.ChAdOx1 nCoV-19 recipients had a significantly lower viral load as represented byminimum PCR Ct value (pInterpretation: Efficacy of ChAdOx1 nCoV-19 against the B.1.1.7 variant of SARS-CoV-2 is similar to the efficacy of the vaccine against other lineages. Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease.Trial Registration Number: This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137.Funding: The clinical trial was funded by UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR OxfordBiomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome SangerInstitute. Computational work was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with funding from the NIHR Oxford BRC.Conflict of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patentapplication covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP and SNF are NIHR SeniorInvestigators. AVSH is a cofounder of and consultant to Vaccitech and is named as aninventor on a patent covering design and use of ChAdOx1-vectored vaccines(PCT/GB2012/000467). MDS reports grants from Janssen, GlaxoSmithKline, Medimmune,Novavax, and MCM Vaccine and grants and non-financial support from Pfizer outside of the submitted work. CG reports personal fees from the Duke Human Vaccine Institute outside of the submitted work. ADD reports grants and personal fees from AstraZeneca outside of the submitted work. SNF reports grants from Janssen and Valneva, outside the submitted work.TLV and JV are employees of AstraZeneca. All other authors declare no competing interests.The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.Ethical Approval: The study was sponsored by the University of Oxford (Oxford, UK) and approved in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) reference 21584/0428/001-0001 and the South-Central Berkshire Research Ethics Committee reference 20/SC/0179.

Safety and Immunogenicity of the ChAdox1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in HIV Infection

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine is immunogenic and protects against COVID-19. However, data on vaccine immunogenicity are needed for the 40 million people living with HIV (PWH), who may have less functional immunity and more associated co-morbidities than the general population. Methods: Between the 5th and 24th November 2020, 54 adults with HIV, aged 18-55 years, were enrolled into a single arm open label vaccination study within the protocol of the larger phase 2/3 COV002 trial. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses (5 × 1010 vp) was given 4-6 weeks apart. All participants were on antiretroviral therapy (ART) with undetectable plasma HIV viral loads and CD4+ T cell counts >350 cells/µl at enrolment. Data were captured on adverse events. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo interferon-γ enzyme-linked immunospot assay (ELISpot) and T cell proliferation. All outcomes were compared with a HIV uninfected group from the main COV002 study.Findings: 54 participants with HIV (median age 42.5 years (IQR 37.2-49.8)) received two doses of ChAdOx1 nCoV-19. Median CD4+ T cell count at enrolment was 694 cells/µl (IQR 562-864). Results are reported for 56 days of follow-up. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (49%), fatigue (47%), headache (47%), malaise (34%), chills (23%), and muscle or (36%) joint pain (9%), the frequencies of which were similar to the HIV-negative participants. There were no serious adverse events. Anti-spike IgG responses by ELISA peaked at Day 42 (median 1440 ELISA units, IQR 704-2728) and were sustained out to Day 56. There was no correlation with CD4+ T cell count or age and the magnitude of the anti-spike IgG response at Day 56 (P>0.05 for both). ELISpot and T cell proliferative responses peaked between Day 14 and 28 after prime and were sustained through to Day 56. When compared to participants without HIV there was no statistical difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (P>0.05 for all analyses).Interpretation: In this study of PWH, vaccination with ChAdOx1 nCoV-19 was well tolerated and there was no difference in humoral and cell-mediated immune responses compared to an adult cohort without HIV who received the same vaccination regime. Trial Registration: Trial Registration number is NCT04400838. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Declaration of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). AstraZeneca reviewed the data from the study and the final manuscript before 474 submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (a collaborator in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AVSH is a cofounder of and consultant to Vaccitech and is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467).Ethical Approval: Written informed consent was obtained from all participants, and the trial was done in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. This study was approved in the UK by the Medicines and Healthcare products Regulatory Agency (reference 21584/0424/001-0001) and the South Central Berkshire Research Ethics Committee (reference 20/SC/0145). Vaccine use was authorised by Genetically Modified Organisms Safety Committees at each participating site.

Duration of Effectiveness of Vaccines Against SARS-CoV-2 Infection and COVID-19 Disease: Results of a Systematic Review and Meta-Regression

Background: Knowing whether and to what extent COVID-19 vaccine effectiveness wanes is critical to informing vaccine policy, such as the need for and timing of booster doses. Methods: We performed a systematic review from June 17 to October 27, 2021, using a structured search strategy of multiple databases. Studies with vaccine efficacy or effectiveness (VE) estimates for any WHO Emergency-Use-Listed COVID-19 vaccine at discrete time intervals after full vaccination and meeting pre-defined screening criteria underwent full-text review and risk of bias assessment. Random effects meta-regression was used to estimate the average change in VE from one to six months after full vaccination. Findings: Of 9,261 studies screened, 217 underwent full text review, and 14 were included in analyses. Vaccines evaluated were Pfizer/BioNTech-Comirnaty (n=11), Moderna-mRNA-1273 (n=8), Janssen-Ad26.COV2.S (n=3), and AstraZeneca-Vaxzevria (n=2). On average, VE against SARS-CoV-2 infection decreased between 1 and 6 months after full vaccination by 18·5 percentage points (95% CI 8·4-33·4, p=0·0006) among persons of all ages and 19·9 percentage points (95% CI 9·2-36·7, p=0·0007) among older persons; for symptomatic COVID-19 disease, VE decreased by 25·4 (95% CI 13·7-42·5) and 32·0 percentage points (95% CI 11·0-69·0), respectively; and for severe COVID-19 disease, VE decreased by 8·0 (95% CI 3·6-15·2) and 9·7 percentage points (95% CI 5·9-14·7), respectively. The majority of VE estimates against severe disease remained over 70% for all time points. Interpretation: COVID-19 vaccine efficacy or effectiveness against COVID-19 severe disease remained high (>70%) in most studies in the six months after full vaccination, although it did decrease some (on average, 8-10 percentage points) between one and six months after full vaccination. In contrast, VE against SARS-CoV-2 infection and symptomatic COVID-19 disease decreased approximately 20-30 percentage points during the six months after vaccination. The decrease in VE is likely due, at least in part, to waning immunity, although we cannot rule out the effect of bias. Continued follow-up of VE beyond six months is critical for updating COVID-19 vaccine policy. . Funding Information: Coalition for Epidemic Preparedness Innovations (CEPI)Declaration of Interests: MMH reports research grants from World Health Organization (WHO, Coalition for Epidemic Preparedness Innovations (CEPI), Asian Development Bank (ADB), Bill & Melinda Gates Foundation (BMGF), and Pfizer (all paid to the institution). RA reports a contract from the United States Centers for Disease Control and Prevention, a grant from the Chile Ministry of Science, and consulting fees from Mayo Clinic and Chile Ministry of Health. YG reports research grants from the United States-Israel Binational Science Foundation (BSF) and Israel Science Foundation. MJG reports research grants from South African Medical Research Council and BMGF (all paid to the institution) and participation on a data safety monitoring board for a study on the effectiveness of COVID-19 vaccination against SARS-CoV-2-associated hospitalization and death. AH reports research grants from United States-Israel BSF. KLO serves as the Secretariat for the WHO Strategic Advisory Group of Experts on Immunization. MDK reports research grants from WHO, CEPI, ADB, and Pfizer (all paid to the institution) and consultancy fees from Merck. All other authors have nothing to declare.

How Australia's commitment and activities for measles control achieved rubella elimination

Background: The global measles and rubella strategic plan 2012–20 has a target for measles and rubella elimination in five WHO regions by the end of 2020. Only one region has eliminated rubella. The WHO Strategic Advisory Group of Experts on Immunization advised rubella control was lagging and recommended rubella vaccination be introduced into all country immunisation programmes as soon as possible. We describe the impact enhanced measles control activities, using measles-mumps-rubella (MMR) vaccines, had on rubella incidence in Australia and how these activities lead to the successful elimination of both viruses. Methods and materials: We reviewed rubella notifications from Australia's National Notifiable Disease Surveillance System (1991–2018) and stratified by age, sex and vaccination status. Three-year cumulative incidences were calculated by birth-cohort to assess the impact of two major measles immunisation activities in Australia; the 1998 Measles Control Campaign (MCC), targeted children 5–12 years; and the 2001 Young Adult MMR immunisation program (YA-MMR), targeted adults 18–30 years. MMR immunisation coverage estimates were extracted and compared with notification data. Aggregate national serological survey data (1999, 2002, 2007 and 2012) was assigned to birth-cohorts and the mean, median and ranges of age-group estimates were calculated. Results: The MCC attained 96% coverage, the three-year cumulative incidence of rubella declined by 90% compared with the three years preceding. This effect was also seen following the YA-MMR with a 73% decline in pre-and-post three-year periods, however vaccine coverage during this campaign was considerably lower. Serological surveys displayed a high and constant level of immune protection among females, but males were estimated to have 4–13% lower immunity. Rubella immunity significantly benefited by a direct 17% boost in serological immunity in those 6–11 years of age in the 1999 pre-and-post serological survey. Conclusion: The use of combined MMR vaccines to address measles immunity concerns in Australia demonstrated a symbiotic benefit in not only controlling and eliminating measles transmission but rubella as well. Although the coverage of the YA-MMR was considered to be “sub-optimal”, it effectively closed the rubella immunity gap in Australia, and demonstrates that utilising combination MR-containing vaccines in routine and mass vaccination programs is effective in eliminating the transmission of both viruses.

Optimising dengue pre-vaccination screening

Optimising dengue pre-vaccination screening

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique.

BackgroundThe monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2.MethodsWe conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9–22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p).ResultsWe enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%–62.1%) and 60.6% (52.2%–68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, −5.0% to 19.0%).ConclusionA small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.