Report from the World Health Organization's immunization and vaccines related implementation research advisory committee (IVIR-AC) meeting, Geneva, 11-13 September 2023.

Evaluating vaccine-related research is critical to maximize the potential of vaccination programmes. The WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) provides an independent review of research that estimates the performance, impact and value of vaccines, with a particular focus on transmission and economic modelling. On 11-13 September 2023, IVIR-AC was convened for a bi-annual meeting where the committee reviewed research and presentations across eight different sessions. This report summarizes the background information, proceedings and recommendations from that meeting. Sessions ranged in topic from timing of measles supplementary immunization activities, analyses of conditions necessary to meet measles elimination in the South-East Asia region, translating modelled evidence into policy, a risk-benefit analysis of dengue vaccine, COVID-19 scenario modelling in the African region, therapeutic vaccination against human papilloma virus, the Vaccine Impact Modelling Consortium, and the Immunization Agenda 2030 vaccine impact estimates.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Measles in the 21st Century: Progress Toward Achieving and Sustaining Elimination.

The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles.

Ensuring Equitable Access To COVID-19 Vaccines In The US: Current System Challenges And Opportunities.

There has been a worldwide effort to accelerate the development of safe and effective vaccines for severe acute respiratory syndrome coronavirus-2. When vaccines become licensed and available broadly to the public, the final hurdle is equitable distribution and access for all who are recommended for vaccination. Frameworks and existing systems for allocation, distribution, vaccination, and monitoring for safety and effectiveness are assets of the current immunization delivery system that should be leveraged to ensure the equitable distribution and broad uptake of licensed vaccines. The system should be strengthened to address gaps in access to immunization services and to modernize the public health infrastructure. We offer five recommendations as guideposts to ensure that policies and practices at the federal, state, local, and tribal levels support equity, transparency, accountability, availability, and access to coronavirus disease 2019 vaccines.

Challenges in estimating influenza vaccine effectiveness.

Introduction: Influenza vaccination is regarded as the most effective way to prevent influenza infection. Due to the rapid genetic changes that influenza viruses undergo, seasonal influenza vaccines must be reformulated and re-administered annually necessitating the evaluation of influenza vaccine effectiveness (VE) each year. The estimation of influenza VE presents numerous challenges. Areas Covered: This review aims to identify, discuss, and, where possible, offer suggestions for dealing with the following challenges in estimating influenza VE: different outcomes of interest against which VE is estimated, study designs used to assess VE, sources of bias and confounding, repeat vaccination, waning immunity, population level effects of vaccination, and VE in at-risk populations. Expert Opinion: The estimation of influenza VE has improved with surveillance networks, better understanding of sources of bias and confounding, and the implementation of advanced statistical methods. Future research should focus on better estimates of the indirect effects of vaccination, the biological effects of vaccination, and how vaccines interact with the immune system. Specifically, little is known about how influenza vaccination impacts an individual's infectiousness, how vaccines wane over time, and the impact of repeated vaccination.

Achieving an Optimal Childhood Vaccine Policy.

Policies to remove parents' ability to opt-out from school immunization requirements on the basis of religious or personal beliefs (ie, nonmedical exemptions) may be a useful strategy to increase immunization rates and prevent outbreaks of vaccine-preventable disease. However, there is uncertainty about the effectiveness of this strategy and the range of possible outcomes. We advocate for a more deliberative process through which a broad range of outcomes is scrutinized and the balance of values underlying the policy decision to eliminate nonmedical exemptions is clearly articulated. We identify 3 outcomes that require particular consideration before policies to eliminate nonmedical exemptions are implemented widely and outline a process for making the values underlying such policies more explicit.

Polio endgame: the global introduction of inactivated polio vaccine.

In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses.