New studies look at the broader impact of vaccines

In July of 2017 the Value of Vaccination Research Network (VoVRN) issued a call for concept notes focused on the broader social and economic impact of vaccination. Out of the 30 concept notes received, the VoVRN requested full proposals from six study teams. After a rigorous review of those proposals involving the VoVRN’s Secretariat, members of the Steering Committee, and external expert reviewers, the VoVRN identified three studies to recommend for funding. The VoVRN also identified one pilot study for funding that emerged during the initial call for concept notes. Finally, a Harvard-led research team will conduct an additional study under the auspices of the VoVRN. These projects are supported by a grant from the Bill & Melinda Gates Foundation.

Collectively, these exceptionally promising studies cover a range of methodologies, geographies, pathogens, and vaccines. The VoVRN is happy to announce the following projects:

  • Ramanan Laxminarayan (Center for Disease Dynamics, Economics & Policy) — The effects of vaccine introduction on health, wellbeing, antimicrobial consumption and resistance.

  • Saad Omer (Emory University) — The Broader Impact of Maternal Immunization in Sub-Saharan Africa and Asia: a multisite study in randomized clinical control trial cohorts.

  • Stephen Elledge (Brigham and Women’s Hospital & Harvard Medical School) — Elucidating the extra dividends of vaccination

  • Anita Shet (Johns Hopkins Bloomberg School of Public Health) — Immunization Impact on Cognition Outcomes and School Monitoring Outcomes Study (I-COSMOS): A pilot study in India.

  • JP Sevilla & David Bloom (Harvard T.H. Chan School of Public Health) — Development and application of a comprehensive model for the full social and economic benefits of vaccines.

Please see below for a brief summary of each project.

Ramanan Laxminarayan — Center for Disease Dynamics, Economics & Policy

The effects of vaccine introduction on health, wellbeing, antimicrobial consumption and resistance

With an annual birth cohort of over 27 million infants, India has recently undertaken major steps towards modernizing its Universal Immunization Program (UIP) and expanding its vaccine portfolio. Three major developments since 2014 merit attention. First, new vaccines have been introduced into the UIP. Second, a grant has enabled India to make major investments in improving the vaccine “cold chain” and vaccine delivery. Third, Mission Indradhanush (a Government of India health mission that aims to immunize more than 90% of children by December 2018) has already resulted in a roughly 10 percentage point increase in full‐immunization coverage rates. Meanwhile, India is burdened by the increasing prevalence of resistant pathogens and rising rate of untreatable neonatal sepsis and healthcare-associated infections. These are a consequence of poor public health systems, high background rates of infectious diseases (including healthcare-associated infections), easy, prescription-free access to inexpensive antimicrobials, and rising incomes. Vaccines, particularly those against pneumococcal pneumonia and seasonal influenza, have been responsible for reducing antimicrobial consumption in developed countries.

This study will use spatial and temporal variations in the introductions of the rotavirus vaccine, Haemophilus infuenzae type b-containing pentavalent vaccine, and pneumococcal conjugate vaccine to statistically estimate the impact of vaccine introduction on antimicrobial consumption. Data obtained from these rollouts will be used to parameterize IndiaSim, an agent‐based microsimulation model that will be upgraded to incorporate transmission dynamics for the purpose of this study. With these two approaches, the researchers aim to study the effects of vaccine introduction on (1) respiratory and diarrheal diseases and (2) antimicrobial use and resistance. Researchers will measure the number of incident cases, deaths, disability‐adjusted life years, out‐of‐pocket treatment expenditure, and use of antimicrobials and associated costs that would be averted by scale‐up of the vaccines in India.

Saad Omer — Emory University

The broader impact of maternal immunization in Sub-Saharan Africa and Asia: a multisite study in randomized clinical control trial cohorts

Maternal immunization prevents disease and adverse outcomes among pregnant women and their young infants during a period of substantial neurological development. There is evidence that interventions, such as infant and childhood vaccination, lead to improved cognitive development and educational attainment. Therefore, maternal immunization could potentially have large benefits with respect to cognitive development and educational outcomes that are both measurable and monetizable. The WHO recommends that countries implementing seasonal influenza vaccination give the highest priority to pregnant women. Despite this recommendation, few low- and middle-income countries regularly vaccinate pregnant women against influenza. While mortality and morbidity data have been useful for the justification of conducting research on conventional outcomes, they have not been sufficient to influence the universal introduction of maternal influenza immunization programs.

This study will assess the broad benefits of maternal immunization in South Africa and Bangladesh. Using established cohorts from randomized clinical controlled trials of maternal influenza immunization, researchers will estimate the association between maternal immunization status and productivity gains related to cognitive outcomes (measured through standardized test scores) and educational outcomes (measured through school attainment and/or enrollment). This study will be the first to assess the impact of maternal immunization on educational and cognitive outcomes across multiple sites and age groups. The high-quality data from this study will inform evidence-based decision making with respect to global maternal vaccination policy and investment strategies for influenza and other maternal vaccine targets.

Stephen Elledge — Brigham and Women’s Hospital & Harvard Medical School

Elucidating the extra dividends of vaccination

Vaccines, especially live vaccines, appear to have a strong heterologous capacity to reduce disease due to non-vaccine pathogens. The WHO SAGE warns that although the heterologous benefits of vaccines to reduce off-target infections appear to be important (with extra gains that may exceed even the primary vaccine effects), a lack of biological evidence impedes incorporation of these benefits into formal vaccine assessments. It is hypothesized that observed health benefits emanate from boosted heterologous antibody responses elicited by live vaccination and, in the case of measles vaccine, preservation of immune memory by preventing measles-induced immune deletion. 

This study aims to elucidate the biological underpinnings of improved survival following vaccine introductions by quantifying and mapping the entire antibody repertoire in curated sets of paired clinical serum samples. These samples were collected longitudinally before and after natural measles infections (i.e., measles), or vaccination (with BCG, LAIV, or routine childhood vaccines between 0-18 months of age). By coupling the biology with detailed and robust ecological models of measles and non-measles infectious-disease mortality across populations and over multiple decades spanning the introductions of measles vaccines, the study team will formally quantify the broad benefits of measles vaccination on childhood health, and the long-term labor-market gains accrued from formal inclusion of these benefits in vaccine assessments.

Anita Shet — Johns Hopkins Bloomberg School of Public Health

Immunization Impact on Cognition Outcomes and School Monitoring Outcomes Study (I-COSMOS): A pilot study in India

This pilot will evaluate the feasibility of a study to assess the link between complete childhood immunization and cognitive outcomes by leveraging the phased pneumococcal conjugate vaccine (PCV) rollout in India from 2017-2020. The research team will assess the viability of enrolling children (ages 12-18 months and 24-30 months) from the Palwal district in Haryana, obtaining valid health and school records, performing cognitive assessments, and retaining children and caregivers. Researchers will track physical growth, health outcomes (e.g., hospitalizations and clinic visits), and educational outcomes (e.g., school enrollment, rate of dropout, and absenteeism) among enrolled children. The pilot also involves administering questionnaires to the caregivers of enrolled children to assess their perception of the value of vaccines (including perceived health and economic benefits) and their experiences with immunization clinic visits.

The study hypothesis is that complete immunization in early childhood (1-2 years of age) contributes to improvements in early cognitive development and educational attainment. Complete immunization can improve cognitive outcomes in children via two main pathways: first, by preventing ill health due to infections, and second, by allowing children access to preventative healthcare and nutritional services during their regularly scheduled immunization visits to healthcare facilities. Through a quasi-experimental design, researchers will compare children in PCV-rollout districts to children in adjacent, non-PCV-introduction districts.

J.P. Sevilla & David Bloom — Harvard T.H. Chan School of Public Health

Development and application of a comprehensive model for the full social and economic benefits of vaccines

This research aims to deliver to health and economic policymakers rigorous evidence on the full social and economic benefits of different vaccines. It aims to put that evidence in readily accessible, understandable, and actionable forms such as benefit-cost ratios and social rates of return on investment.

Researchers will develop a model to estimate the full social and economic benefits of a specific vaccine, or package of vaccines, for a given context. Once developed, the model will be applied to a specific country setting. Countries of primary interest for early application of the model are those that have recently transitioned from Gavi support, and those that will do so in the coming years, and need to make difficult decisions concerning which immunization programs to fund independently. Researchers will also apply the model to representative Gavi-supported countries in order to help Gavi and other international donors rationally assess which new vaccinations are likely to provide the greatest returns on investment. This project will also create an easy-to-use software program that will enable policymakers and others to apply the model to different vaccines and country contexts.