Sanguine Connections: The Benefits of Longitudinal Vaccine Studies

July 26, 2024

Welcome to Sanguine Connections, exploring the process, challenges, and nuances of biospecimen procurement for translational studies.

Charting Immunity: The Benefits of Longitudinal Vaccine Studies

As flu season approaches, we are reminded of the importance of vaccines to protect against not only the flu but a myriad of infectious diseases. Understanding the underlying mechanisms that make vaccines effective is key, and one critical aspect for this research involves studying biological samples, often blood, collected before and after vaccination. These biospecimens provide invaluable insights and benefits, some of which are explored in this blog where we discuss the essentials of baseline data, examine notable longitudinal vaccine studies, and consider the unique challenges and successes of prospective collections for vaccine research.

The essentials of baseline data

Baseline or pre-vaccine samples establish a reference point in immunological studies. These samples enable researchers to understand an individual’s initial immune status. By comparing baseline samples with those taken post-vaccination, researchers can discern changes attributable to the vaccine, such as the activation of a specific immune pathway or the production of an antibody. These types of studies are important for determining efficacy of a new vaccine, identifying biomarkers for immune response, and studying population-specific differences in vaccine effectiveness. Additionally, comparing pre- and post-vaccination samples can be utilized in safety monitoring by recognizing adverse reactions or unanticipated effects.

Examples of longitudinal vaccine studies in the literature

Evaluation of antibody binding of influenza vaccine over multiple years

Researchers from University of Georgia tracked the antibody response to the flu vaccine over six consecutive flu seasons. Their cohort of hundreds was aimed to provide a broader understanding of differences in immune response based on age and comorbidities. This large scale effort took blood samples at time of vaccination, as well as three to five timepoints post vaccination. The team found a number of factors that contribute to the vaccine induced immune response including age, health status, and history to exposure. Further omic studies are being performed to build predictive models for host response and vaccine effectiveness.

Analysis of immune response to mRNA SARS-CoV-2 vaccine in older adults

One of many longitudinal studies focused on COVID-19 was published by Ravussin et al. and focused on response to the mRNA vaccine in older adults across multiple doses. As the older population is at higher risk of severe COVID-19 and death, they were prioritized for vaccination during the pandemic. Development of antibodies and antibody level can be reduced with age, as well as comorbidities, suggesting a need for a deeper understanding of this population’s immune response to vaccination. A combination of analysis of blood, medical records, and questionnaires before vaccination, after dose two, and after dose three, produced extensive data for analysis. Although the authors mention limitations in diversity to the cohort including under-representation of individuals with frailties and chronic conditions, they were able to characterize the immune response and highlight associations with the response and lifestyle and comorbidities. For example, in agreement with other studies, there is a correlation between hypertension and poorer antibody response to vaccination.

Assessment of antibody protection for the flu in breastmilk

Often lactating women are excluded from clinical trials for good reasons – particularly around concerns of safety for the infant and that physiological changes can make it more challenging to interpret results. A team from Mount Sinai examined the protection against the flu for breast-fed infants by assessing the level of antibodies in seasonally-relevant hemagglutinin- specific antibodies in breastmilk. Lactating women provided samples of milk prior to and 2 weeks post receiving the seasonal flu vaccine. The study found that in the cohort of New York residents that participated, that although they could measure IgG, sAb, and IgG HA titers in the breast milk, these titers were not significantly boosted post vaccine. The only exception was an HA immunogen that had been included the last several years as opposed to others which were new to the vaccine at the time of study. The authors suggest vaccination development include this population for identifying effective passive protection through breast milk.

Challenges for longitudinal vaccine studies

With the examples above and across vaccine studies, a few challenges are common including often wanting a diverse cohort, multiple collection time points (with sometimes multiple types of samples taken), and additional health information. Sanguine is ready to tackle these challenges with our vast donor network across the US. Below is one example of a successful vaccine study where a biopharma company focused on immunology and virology partnered with Sanguine to carry out a flu vaccination study.

The study required 50 healthy adults from age 18 to 80, who planned to receive that year’s flu vaccine. Participation involved two visits – one within a month prior to being vaccinated and the second two to four weeks post-vaccination. Sanguine recruited across the country for in-home collections, enabling the donors to schedule visits at their convenience.

Whole blood and saliva were collected on the first visit, and only blood at the second visit. Plasma isolation was performed on a portion of the whole blood and both samples were sent to the biopharma company for further analysis. The salvia was sent to Sanguine for HLA-typing.

In addition to sample collection, a custom questionnaire was created that focused on general vaccination history, COVID-19 infection history, and general demographics.

With 98 of the 100 planned visits completed to the full plan, extensive donor data, and multiple sample collection, this prospective collection provided significant data for the scientists to address their research questions.

Longitudinal studies are indispensable for advancing our understanding of vaccine efficacy and safety. By collecting multiple time points and comprehensive donor data, researchers can uncover critical insights into immune responses, identify novel biomarkers, and monitor potential adverse or unexpected reactions. Challenges arise including diversity of cohorts, retaining participation, and comprehensive donor data. Sanguine’s innovative direct-to-donor model enables us to overcome these obstacles, and provide invaluable support to the virology community.