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"Sullivan, Sheena G"
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Comparative duration of neutralizing responses and protections of COVID-19 vaccination and correlates of protection
The decline in neutralizing antibody (nAb) titers and vaccine efficacy /effectiveness (VE) for SARS-CoV-2 vaccines has been observed over time and when confronted with emerging variants, two factors that are hard to distinguish. Despite substantial drop in nAb titers against Omicron, VE remains high for severe cases and fatalities, raising questions about the utility of detected nAbs as a correlate of protection for COVID-19 vaccines for varying disease severity. Here, we conducted a systematic comparison of waning dynamics of nAb and VE over time and against variants with varying levels of disease severity. Using Bayesian linear regression models, we found that antigenically-shifted variants, like Omicron, could potentially lead to greater reductions in nAb titers and primary VE against mild infections than associated immunity waning observed over a 180-day period. By comparing model predicted nAb titers and VE on the same time scales, we found that VE against severe and fatal outcomes remained above 75% even when nAb titers reached the detectable limit of assays, despite strong correlations with nAb titers (spearman correlations ≥0.7) across variants over time. This finding suggested detectable nAb titers are not always sensitive enough to fully predict protection against severe disease and death from SARS-CoV-2.
Neutralizing antibody titers are considered possible correlates of protection against SARS-CoV-2, but vaccine efficacy for Omicron infections is high despite reduced titers. Here, the authors investigate the relationship between neutralizing antibody titers and vaccine effectiveness/efficacy through a meta-analysis and statistical modeling.
Journal Article
Key Challenges for Respiratory Virus Surveillance while Transitioning out of Acute Phase of COVID-19 Pandemic
To support the ongoing management of viral respiratory diseases while transitioning out of the acute phase of the COVID-19 pandemic, many countries are moving toward an integrated model of surveillance for SARS-CoV-2, influenza virus, and other respiratory pathogens. Although many surveillance approaches catalyzed by the COVID-19 pandemic provide novel epidemiologic insight, continuing them as implemented during the pandemic is unlikely to be feasible for nonemergency surveillance, and many have already been scaled back. Furthermore, given anticipated cocirculation of SARS-CoV-2 and influenza virus, surveillance activities in place before the pandemic require review and adjustment to ensure their ongoing value for public health. In this report, we highlight key challenges for the development of integrated models of surveillance. We discuss the relative strengths and limitations of different surveillance practices and studies as well as their contribution to epidemiologic assessment, forecasting, and public health decision-making.
Journal Article
Effectiveness of International Travel Controls for Delaying Local Outbreaks of COVID-19
During the coronavirus disease pandemic, international travel controls have been widely adopted. To determine the effectiveness of these measures, we analyzed data from 165 countries and found that early implementation of international travel controls led to a mean delay of 5 weeks in the first epidemic peak of cases.
Journal Article
Influenza Vaccine Effectiveness in Australia During 2017–2019
ABSTRACT
Background
Vaccine effectiveness (VE) estimates provide important post‐marketing assessment of how well seasonal influenza vaccines prevent medically attended influenza disease. We present VE estimates for primary care in Australia for the 2017–2019 seasons.
Methods
The study used a test‐negative design. Influenza VE was estimated from adjusted logistic regression models comparing the odds of vaccination among influenza‐test‐positive cases and test‐negative non‐cases. Estimates were made overall and separately by influenza type, subtype, lineage and clade and stratified by age group. Antigenic similarity of influenza viruses to vaccine strains was assessed using the haemagglutination inhibition assay, and phylogenetic analysis was performed on sequenced viruses.
Results
The study included 2879, 1973 and 3371 general practice patients with swabs collected during 2017, 2018 and 2019 respectively. Influenza A(H3N2) was predominant in 2017 and 2019, while influenza A(H1N1)pdm09 predominated in 2018. VE was estimated at 37% (95% CI 22, 48) for the 2017 season, 53% (95% CI 33, 67) for 2018 and 50% (95% CI 40, 58) for 2019. In general, estimates were higher against A(H1N1)pdm09 and influenza B viruses and lower against A(H3N2) viruses. Across the three seasons, antigenic data identified a greater proportion of A(H1N1)pdm09 and influenza B viruses than A(H3N2) viruses as antigenically similar to the cell‐propagated reference viruses. VE estimates by clade generally indicated higher VE among viruses in the same clade as the vaccine viruses.
Conclusions
Influenza VE varied across influenza seasons and by influenza type/subtype. Given the ongoing evolution of circulating influenza viruses, vaccine improvements are needed, especially for influenza A(H3N2).
Journal Article
Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines
Vaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals.
Using in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type.
Our analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens.
Reconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.
Journal Article
Estimated Relative Effectiveness and Public Health Impact of Cell‐Based Versus Egg‐Based Influenza Vaccines During the 2022–2023 Season in the United States
Egg adaptation can reduce the effectiveness of egg-based influenza vaccines. Previous studies have demonstrated improved effectiveness of cell versus egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) during the 2017-2020 influenza seasons among persons aged ≥ 4 years. Here we evaluate the relative vaccine effectiveness (rVE) of QIVc versus QIVe in preventing test-confirmed influenza among persons aged 6 months to 64 years during the US 2022-2023 influenza season, along with the potential impact on influenza burden averted.
A retrospective test-negative design was applied to linked electronic health records and claims data from QIVc or QIVe recipients who were tested for influenza in routine outpatient care within 7 days of an acute respiratory or febrile illness. rVE was estimated by comparing the odds of testing positive among QIVc versus QIVe recipients, adjusted using doubly robust methodology. The influenza burden additionally averted by vaccination with QIVc versus QIVe was estimated using a published model.
Of 43,086 patients included, 18.6% received QIVc and 81.4% received QIVe. The rVE of QIVc versus QIVe was 7.7% (95% CI, 0.9%-13.9%). Use of QIVc instead of QIVe during the 2022-23 influenza season would have prevented an additional 636,209 symptomatic cases of influenza, 314,130 outpatient visits, and 3759 hospitalizations.
QIVc was superior to QIVe in the prevention of test-confirmed influenza among persons aged 6 months to 64 years during the US 2022-2023 influenza season. The rVE of 7.7% would translate to a substantially reduced influenza burden if QIVc were used over QIVe.
Journal Article
Burden, effectiveness and safety of influenza vaccines in elderly, paediatric and pregnant populations
Vaccination is the most practical means available for preventing influenza. Influenza vaccines require frequent updates to keep pace with antigenic drift of the virus, and the effectiveness, and sometimes the safety, of the vaccine can therefore vary from season to season. Three key populations that the World Health Organization recommends should be prioritized for influenza vaccination are pregnant women, children younger than 5 years of age and the elderly. This review discusses the burden of influenza and the safety and effectiveness profile of influenza vaccines recommended for these groups.
Journal Article
Evolution of China's response to HIV/AIDS
Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS—the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.
Journal Article
Meeting Report From “Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned From the COVID‐19 Pandemic”
ABSTRACT
Background
This report summarizes the discussions and conclusions from the “Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID‐19 Pandemic” meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023.
Conclusions
Discussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID‐19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection.
Journal Article