Pandemic Vaccine Research Articles

Socioeconomic Differences in SARS-CoV-2 Infection and Vaccination in Germany: A Seroepidemiological Study After One Year of COVID-19 Vaccination Campaign.

Objective: To evaluate the socioeconomic patterns of SARS-CoV-2 antigen contacts through infection, vaccination or both ("hybrid immunity") after 1year of vaccination campaign. Methods: Data were derived from the German seroepidemiological Corona Monitoring Nationwide study (RKI-SOEP-2; n = 10,448; November 2021-February 2022). Combining serological and self-report data, we estimated adjusted prevalence ratios (PR) of SARS-CoV-2 infection, COVID-19 vaccination, basic immunization (at least two SARS-CoV-2 antigen contacts through vaccination and/or infection), and three antigen contacts by education and income. Results: Low-education groups had 1.35-times (95% CI 1.01-1.82) the risk of SARS-CoV-2 infection compared to high-education groups. COVID-19 vaccination (at least one dose) and basic immunization decreased with lower education and income. Low-education and low-income groups were less likely to have had at least three antigen contacts (PR low vs. high education: 0.74, 95% CI 0.65-0.84; PR low vs. high income: 0.66, 95% CI 0.57-0.77). Conclusion: The results suggest a lower level of protection against severe COVID-19 for individuals from low and medium socioeconomic groups. Pandemic response and vaccination campaigns should address the specific needs and barriers of these groups.

Exploring and contextualizing the associations among political identification, vaccine risk and benefit perceptions, and vaccine acceptance.

There is considerable research on the influence of political partisanship on vaccine acceptance. However, the current study is one of the first to investigate how political identification is related to risk and benefit perceptions vis-à-vis vaccines. Based on survey data collected in the United States regarding four different vaccines at three points in time (n=383 for April-June 2012; n=364 for March 2020; n=334 for April-May 2020), Democrats were found to have more positive attitudes toward vaccinations in general and hold more favorable risk and benefit perceptions of pandemic and routine vaccines overall compared to Republicans. However, the onset of a pandemic can serve as an equalizing force and motivate similar risk and benefit perceptions across party lines, but this force can wane quickly when the information environment is politicized. For political partisans who are ideologically oriented to be more hesitant toward vaccines, two conditions can help sustain their favorable vaccine perceptions during a pandemic: (a) when they identify with the governing political party, and (b) when there are consistent reassurances of vaccine safety and effectiveness from their partisan leadership. Given that risk and benefit perceptions were found to be consistently associated with vaccine acceptance across contexts in this study, communication aimed at encouraging vaccinations should always address the risks and benefits of a vaccine in ways that are tailored for individuals with different political affiliations.

West Australian parents’ views on vaccinating their children against COVID-19: a qualitative study

BackgroundAustralian children and adolescents were among the last local cohorts offered COVID-19 vaccines. Despite promising initial uptake, coverage subsequently plateaued, requiring further efforts to improve access and build parents’ recognition of the importance of COVID-19 vaccination. We sought to understand West Australian (WA) parents’ willingness to vaccinate their children to inform strategies for improving uptake at the time in which they were becoming eligible.MethodsWe undertook in-depth qualitative interviews with 30 parents of children aged 5–17 years from June – December 2021. During this period, children aged 12–15 years became eligible for vaccination; children aged 5–11 years became eligible shortly thereafter. Data were thematically analysed in NVivo.ResultsMost parents intended on vaccinating their children once eligible. Parents sought to protect their children, to protect the community, to resume travel, and to get back to “normal”. They reflected that vaccination against key infectious threats is a routine activity in childhood. Some were concerned about the vaccine, particularly mRNA vaccines, being new technology or impacting fertility. “Wait-awhiles” wanted to see what other parents would do or were delaying until they felt that there was a higher risk of COVID-19 in WA. Most parents of younger children wanted their child to be vaccinated at the general practice clinic due to familiarity and convenience. Parents were particularly eager for clear and consistent messaging about vaccination of children and adolescents, including safety, importance, scientific evidence, and personal stories.ConclusionFor future pandemic vaccinations pertaining to children, governments and health officials need to address parents’ concerns and meet their preferences for the delivery of the vaccine program to children and adolescents.

Genomic analysis of SARS-CoV-2 Circulating during Second and Third Wave of COVID-19 in Nepal.

In Nepal, since the first detection of COVID-19 case in January 2020, the total cases have rose to almost a million with more than 12,000 deaths. Till now, WHO has classified 5 variants of SARS-Cov2 as variant of concerns at different time points causing many waves in different countries and regions at different time points. Nepal had also faced three distinct waves of COVID-19 caused by different variant of COVID 19. The objective of this study was to perform whole-genome sequencing of SARS-CoV-2 circulating in different waves of COVID-19 in Nepal and investigate its variant or lineage. In this study, samples from 49 SARS-CoV-2 infected subjects from May 2021 to January 2022, were investigated. The methodology followed RNA extraction, real-time PCR for confirmation and whole-genome sequencing. The consensus genomes were interpreted with appropriate bioinformatics tools and databases. Sequence analysis of 49 genomes revealed to be of Delta (n=27) and Omicron Variant (n=22). The mutations in the consensus genomes contained the defining mutations of the respective lineages/variants. There were 20 genomes of Omicron sub-lineage BA.2, 1 of BA.1.1 and 1 of B.1.1.529. This study provides concise genomic evidence of presence of Delta and Omicron variant of COVID-19 in Nepal. Delta and Omicron variants were driving the second wave and the third wave of COVID-19 respectively in Nepal. Therefore, the genomic surveillance must be increased to clearly map out the pandemic and strategize vaccination approaches in the country.

Safety of influenza vaccination during pregnancy: a systematic review

ObjectiveWe conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal...

Canada’s National Advisory Committee on immunization: Adaptations and challenges during the COVID-19 pandemic

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs).Canada’s National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance.In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance.

Vaccine microarray patch self-administration: An innovative approach to improve pandemic and routine vaccination rates

The high-density microprojection array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. HD-MAPs provide an alternative to needle and syringe (N&S) vaccination. Additional advantages could include reduced cold-chain requirements, reduced vaccine dose, reduced vaccine wastage, an alternative for needle phobic patients and elimination of needlestick injuries. The drivers and potential benefits of vaccination by self-administering HD-MAPs are high patient acceptance and preference, higher vaccination rates, speed of roll-out, cost-savings, and reduced sharps and environmental waste. The HD-MAP presents a unique approach in pandemic preparedness and routine vaccination of adults. It could alleviate strain on the healthcare workforce and allows vaccine administration by minimally-trained workers, guardian or subjects themselves. Self-vaccination using HD-MAPs could occur in vaccination hubs with supervision, at home after purchasing at the pharmacy, or direct distribution to in-home settings. As a result, it has the potential to increase vaccine coverage and expand the reach of vaccines, while also reducing labor costs associated with vaccination. Key challenges remain around shifting the paradigm from medical professionals administrating vaccines using N&S to a future of self-administration using HD-MAPs. Greater awareness of HD-MAP technology and improving our understanding of the implementation processes required for adopting this technology, are critical factors underpinning HD-MAP uptake by the public.

Denmark, the United States and Canada: Before, during and post vaccination rollout

ObjectivesWe conduct a rapid review of the post-COVID-19 vaccination efforts undertaken by Denmark, the United States, and Canada. The main areas of focus are threefold: 1) To analyze the timeline of the rollout and access/barriers to vaccinations considering the changing dynamics of COVID-19 and the launch of new generation booster-vaccines across the case countries. 2) To examine sociopolitical factors related to this juxtaposition between lower booster acceptance, despite higher rates of initial vaccine series, in each of the three cases. 3) To determine how each country is moving forward with their ongoing COVID-19 strategies for long-term mitigation planning. MethodsWe followed a Most Similar Systems Design (MSSD) framework to select our cases. We analyze country responses amongst high-income, OECD countries, who shared Western or liberal Democracy, with a formal framework of rule of law, presence of a legal authority and the independence of the judiciary, but differ in their rollout and uptake of the vaccine booster. ResultsDespite variation in booster uptake, all three countries’ COVID-19 mitigation responses became more similar over time, and each country experienced lower than expected booster uptake. ConclusionsDecline in booster doses across each country was related to broad declines in concern about the virus in each location. However, cases with higher uptake of the initial series and use of NPIs, in Denmark and Canada, continue to fare better in morbidity and mortality from COVID-19, despite dwindling booster uptake. Public Interest SummaryThis study looks at how three high income western democracies (Denmark, the United States and Canada) handled the COVID-19 pandemic and booster vaccinations. We briefly look at the initial outbreak of the pandemic, contextualize the initial (pre-booster) vaccination uptake and then assess the booster vaccine uptake. We find that although the countries differ in their approach during the initial stages of COVID-19 and vaccination policy, they all share similarly low booster vaccine uptake. Yet, even with a similarly low booster uptake, each of the countries continue to exhibit differences in morbidity, mortality and disparities associated with COVID-19. The implications of this research are clear – providing access to vaccinations, boosters, testing, and treatment are essential in combating inequalities in COVID-19 outcomes. Overlaying these implications is the importance of a continuously updated national strategy for future pandemics is important.

A TLR9 agonist synergistically enhances protective immunity induced by an Alum-adjuvanted H7N9 inactivated whole-virion vaccine

ABSTRACT Antigen sparing is an important strategy for pandemic vaccine development because of the limitation of worldwide vaccine production during disease outbreaks. However, several clinical studies have demonstrated that the current aluminum (Alum)-adjuvanted influenza vaccines fail to sufficiently enhance immune responses to meet licensing criteria. Here, we used pandemic H7N9 as a model virus to demonstrate that a 10-fold lower amount of vaccine antigen combined with Alum and TLR9 agonist can provide stronger protective effects than using Alum as the sole adjuvant. We found that the Alum/CpG 1018 combination adjuvant could induce more robust virus-specific humoral immune responses, including higher total IgG production, hemagglutination-inhibiting antibody activity, and neutralizing antibody titres, than the Alum-adjuvanted formulation. Moreover, this combination adjuvant shifted the immune response toward a Th1-biased immune response. Importantly, the Alum/CpG 1018-formulated vaccine could confer better protective immunity against H7N9 challenge than that adjuvanted with Alum alone. Notably, the addition of CpG 1018 to the Alum-adjuvanted H7N9 whole-virion vaccine exhibited an antigen-sparing effect without compromising vaccine efficacy. These findings have significant implications for improving Alum-adjuvanted influenza vaccines using the approved adjuvant CpG 1018 for pandemic preparedness.

An Advax-CpG adjuvanted recombinant H5 hemagglutinin vaccine protects mice against lethal influenza infection

There is a major unmet need for strategies to improve the immunogenicity of vaccines to protect against highly pathogenic avian influenza strains with pandemic potential. This study tested the ability of adjuvants based on delta inulin (Advax™) alone or combined with a TLR9 agonist (Advax-CpG™) to enhance the immunogenicity of recombinant H5 hemagglutinin antigen expressed in insect cells (rH5HA) to protect mice against lethal influenza infection. The Advax-adjuvanted rH5HA induced high serum hemagglutination inhibition activity, as well as Th1 and Th2 cytokine secreting CD4 and CD8 T cells. Immunization protected mice against a lethal heterosubtypic H5N1 virus challenge. Mice immunized with an Advax-adjuvanted rHA2 stem antigen prepared by enzymatic cleavage of rH5HA produced serum antibodies devoid of hemagglutination inhibition activity, but these anti-HA2 antibodies were nevertheless able to transfer protection against lethal H1N1 or H3N2 infections to naïve mice. We hypothesize that the enhanced protection afforded by Advax-adjuvanted rH5HA may be mediated by the combination of neutralizing antibodies directed at the HA head, anti-HA2 stem antibodies plus memory CD4 + and CD8 + T cells. This outcome supports further development of the Advax-adjuvanted rH5 pandemic influenza vaccine platform.

An Advax-CpG55.2 adjuvanted recombinant hemagglutinin vaccine provides immunity against H7N9 influenza in adult and neonatal mice

There is a major unmet need for strategies to improve the immunogenicity and effectiveness of pandemic influenza vaccines, particularly in poor responder populations such as neonates. Recombinant protein approaches to pandemic influenza offer advantages over more traditional inactivated virus approaches, as they are free of problems such as egg adaptation or need for high level biosecurity containment for manufacture. However, a weakness of recombinant proteins is their low immunogenicity. We asked whether the use of an inulin polysaccharide adjuvant (Advax) alone or combined with a TLR9 agonist (CpG55.2) would enhance the immunogenicity and protection of a recombinant hemagglutinin vaccine against H7N9 influenza (rH7HA), including in neonatal mice. Advax adjuvant induced predominantly IgG1 responses against H7HA, whereas Advax-CpG55.2 adjuvant also induced IgG2a, IgG2b and IgG3 responses, consistent with the TLR9 agonist component inducing a Th1 bias. Advax-CpG55.2 adjuvanted rH7HA induced high serum neutralizing antibody titers in adult mice. In newborns it similarly overcame immune hypo-responsiveness and enhanced serum anti-rH7HA IgG levels in 7-day-old BALB/C and C57BL/6 mice. Immunized adult mice were protected against a lethal H7N9 virus challenge. When formulated with Advax-CpG55.2 adjuvant, greater protection was seen with rH7HA than with inactivated H7 whole virus antigen. Advax-CpG55.2 adjuvanted rH7HA represents a promising influenza vaccine platform for further development.

The Potential Role of SARS-CoV-2 Infection and Vaccines in Multiple Sclerosis Onset and Reactivation: A Case Series and Literature Review.

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.

Why ethical frameworks fail to deliver in a pandemic: Are proposed alternatives an improvement?

In the past decade, numerous ethical frameworks have been developed to support public health decision-making in challenging areas. Before the COVID-19 pandemic began, members of the authorship team were involved in research programmes, in which the development of ethical frameworks was planned, to guide (a) the use of new technologies for emerging infectious disease surveillance; and (b) the allocation of scarce supplies of pandemic influenza vaccine. However, as the pandemic evolved, significant practical challenges emerged that led to our questioning the value of these frameworks. We now believe that a normative instrument, such as a framework, cannot adequately or reliably provide the ethical guidance that needs to be incorporated into public health decision-making during natural disasters or infectious disease emergencies. Recently it has been suggested that there are potentially more dynamic, flexible, and effective ways to navigate decisions involving complex considerations entailed in policies and practices during a public health emergency. In this paper, we first outline the key functions of a public health ethics framework, before describing why we believe it would not be fit for purpose during a crisis. We end by considering whether proposed alternative methods to promote ethical public health decision-making goals have the potential to meet these objectives.

Lessons From COVID-19 for Pandemic Preparedness: Proceedings From a Multistakeholder Think Tank.

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response.

A survey of patient and public perceptions and awareness of SARS-CoV-2-related risks among participants in India and South Africa.

A cross-sectional survey among participants in India and South Africa to explore perceptions and awareness of SARS-CoV-2-related risks. Main outcome measures-proportion of participants aware of SARS-CoV-2, and their perception of infection risks as it related to their views and perceptions on vaccination, i.e., using COVID-19 vaccine uptake as proxy for awareness level. Self-administered questionnaires were used to collect data via web- and paper-based surveys over three months. Pearson's Chi-squared test assessed relationships between variables; a p-value less than 0.05 was considered significant. There were 844 respondents (India: n = 660, South Africa: n = 184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of pandemic information were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively; reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness. In South Africa, vaccine acceptance was associated with improved hand hygiene practices since the pandemic and flu vaccination in the preceding year. No relationship was noted between awareness and practice of infection prevention measures (such as hand hygiene) and socio-demographic factors such as employment status or availability of amenities. Pandemic response and infection prevention and control measures through vaccination campaigns should consider robust public engagement and contextually-fit communication strategies with multimodal, participatory online and offline initiatives to address public concerns, specifically towards vaccines developed for this pandemic and general vaccine hesitancy.

Expanding global vaccine manufacturing capacity: Strategic prioritization in small countries.

The COVID-19 pandemic highlighted significant gaps in equitable access to essential medical countermeasures such as vaccines. Manufacturing capacity for pandemic vaccines, therapeutics, and diagnostics is concentrated in too few countries. One of the major hurdles to equitable vaccine distribution was "vaccine nationalism", countries hoarded vaccines to vaccinate their own populations first which significantly reduced global vaccine supply, leaving significant parts of the world vulnerable to the virus. As part of equitably building global capacity, one proposal to potentially counter vaccine nationalism is to identify small population countries with vaccine manufacturing capacity, as these countries could fulfill their domestic obligations quickly, and then contribute to global vaccine supplies. This cross-sectional study is the first to assesses global vaccine manufacturing capacity and identifies countries with small populations, in each WHO region, with the capacity and capability to manufacture vaccines using various manufacturing platforms. Twelve countries were identified to have both small populations and vaccine manufacturing capacity. 75% of these countries were in the European region; none were identified in the African Region and South-East Asia Region. Six countries have facilities producing subunit vaccines, a platform where existing facilities can be repurposed for COVID-19 vaccine production, while three countries have facilities to produce COVID-19 mRNA vaccines. Although this study identified candidate countries to serve as key vaccine manufacturing hubs for future health emergencies, regional representation is severely limited. Current negotiations to draft a Pandemic Treaty present a unique opportunity to address vaccine nationalism by building regional capacities in small population countries for vaccine research, development, and manufacturing.

Optic Neuritis After COVID-19 Vaccination: An Analysis of the Vaccine Adverse Event Reporting System.

To investigate the association of optic neuritis (ON) after the COVID-19 vaccines. Cases of ON from Vaccine Adverse Event Reporting System (VAERS) were collected and divided into the prepandemic, COVID-19 pandemic, and COVID-19 vaccine periods. Reporting rates were calculated based on estimates of vaccines administered. Proportion tests and Pearson χ 2 test were used to determine significant differences in reporting rates of ON after vaccines within the 3 periods. Kruskal-Wallis testing with Bonferroni-corrected post hoc analysis and multivariable binary logistic regression was used to determine significant case factors such as age, sex, concurrent multiple sclerosis (MS) and vaccine manufacturer in predicting a worse outcome defined as permanent disability, emergency room (ER) or doctor visits, and hospitalizations. A significant increase in the reporting rate of ON after COVID-19 vaccination compared with influenza vaccination and all other vaccinations (18.6 vs 0.2 vs 0.4 per 10 million, P < 0.0001) was observed. However, the reporting rate was within the incidence range of ON in the general population. Using self-controlled and case-centered analyses, there was a significant difference in the reporting rate of ON after COVID-19 vaccination between the risk period and control period ( P < 0.0001). Multivariable binary regression with adjustment for confounding variables demonstrated that only male sex was significantly associated with permanent disability. Some cases of ON may be temporally associated with the COVID-19 vaccines; however, there is no significant increase in the reporting rate compared with the incidence. Limitations of this study include those inherent to any passive surveillance system. Controlled studies are needed to establish a clear causal relationship.

An investigation of the effects of lockdowns and COVID-19 vaccinations in Ireland

Abstract. The COVID-19 pandemic resulted in many deaths and much upheaval worldwide. Public health responses to the pandemic differed greatly between countries. In 2023, as we emerge from the aftermath of the pandemic, it is now timely to assess the impact of specific public health response measures such as lockdowns and vaccinations. This assessment can help inform the development of evidence-based strategies for future public health responses in pandemic scenarios. We describe the implementation of a Bayesian Hierarchical Poisson Regression (BHPR) model to estimate the impact of pandemic response measures and vaccination on all-cause deaths, including COVID-19, in Ireland. We find that the implementation of lockdown measures and an appropriate vaccination timeline were effective in reducing the number of deaths in Ireland by, most likely, reducing the COVID- 19 mortality rate. We believe our approach could be used to assess the impact of pandemic response measures and vaccination in other countries as well where similar data is available.

OPENCORONA: lessons learned from a pandemic vaccine consortium

OPENCORONA: lessons learned from a pandemic vaccine consortium

Covid-19 vaccine roll-out in England: A qualitative evaluation.

The UK was the first country to launch a national pandemic COVID-19 vaccination programme, which was implemented swiftly despite significant vaccine supply constraints. The delivery strategy used a combination of mass vaccination sites operated by NHS secondary care providers and local sites led by Primary Care Networks, and local pharmacies. Despite nation-wide rollout, persistent gaps in coverage continued to affect particular populations, including ethnic minority and marginalised social groups. The study examined sub-national immunisation commissioners and providers' perspectives on how the COVID-19 vaccine programme was operationalised, and how delivery strategies impacted inequalities in access to vaccination services and uptake. The study aimed to inform national programme implementation, sustainability and future pandemic preparedness. Qualitative research was conducted in eight local NHS areas in 4 regions of England. Semi-structured interviews were performed with 82 sub-national NHS and public health vaccine providers and commissioners. England's COVID-19 vaccination programme was described as top down, centralised and highly political. The programme gradually morphed from a predominantly mass vaccination strategy into more locally driven and tailored approaches able to respond more effectively to inequalities in uptake. Over time more flexibility was introduced, as providers adapted services by "working around" the national systems for vaccine supply and appointment booking. The constant change faced by providers and commissioners was mitigated by high staff motivation and resilience, local collaboration and pragmatism. Opportunities for efficient implementation were missed because priority was given to achieving national performance targets at the expense of a more flexible sub-national tailored delivery. Pandemic vaccination delivery models need to be adapted for underserved and hesitant groups, working in collaboration with local actors. Learnings from the initial COVID-19 vaccine roll-out in England and elsewhere is important to inform future pandemic responses, in tailoring strategies to local communities, and improve large-scale vaccination programmes.