The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination.

Amy C Sherman,Mary Bower,Jennifer Kleinhenz,Christopher Huerta,Vinit Karmali,Muktha S Natrajan,Nadine Rouphael,Lilin Lai,Yongxian Xu,Mark J Mulligan

doi:10.3390/vaccines8040663

Amy C Sherman, Mary Bower + Show 8 more

Open Access

https://doi.org/10.3390/vaccines8040663

Copy DOI

Abstract

(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess for immune factors and mechanisms that impact influenza vaccine responses. (2) Methods: Twenty participants were enrolled into a prospective pilot study based on birth cohort and seasonal influenza immunization history. Immunologic parameters were assessed over a six-month period after the seasonal influenza vaccine was administered. (3) Results: There was no significant imprinting effect, as measured by hemagglutination inhibition (HAI) fold change, HAI geometric mean titer (GMT) for Day 29 or Day 180 post-vaccination and antigen- specific antibody-secreting cells (ASC) for Day 8 post-vaccination. Individuals who had minimal prior seasonal influenza vaccination had a higher magnitude ASC response and a higher HAI fold change post-vaccination than individuals who were repeatedly vaccinated. (4) Conclusions: Repeated seasonal influenza vaccination resulted in a decreased fold change of the immune response, although individuals in this cohort tended to have high HAI titers at baseline that persisted after vaccination. Imprinting effects were not observed in this cohort. These host immune factors should be considered in the development of universal influenza vaccines. ClinicalTrials.gov Identifier: NCT03686514.

Highlights

IntroductionSeasonal influenza outbreaks continue to cause substantial disease burden, with an estimated
Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated3–5 million cases of severe illness, and 290,000 to 650,000 deaths worldwide each year [1]
There is an urgent need to better understand the immunologic responses to current licensed influenza vaccines in order to develop a more effective vaccine that does not rely on annual strain-matched boosters, provides broad protection, and is durable, i.e., a universal influenza vaccine

Summary

Introduction

Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated. 3–5 million cases of severe illness, and 290,000 to 650,000 deaths worldwide each year [1]. In the United States, influenza has resulted in 9–45 million illnesses, with 12,000–61,000 deaths annually since 2010 [2]. Two factors that may affect the immune response to influenza vaccination include imprinting and repeated annual vaccination. In 1960, Francis described the “doctrine of original antigenic sin (OAS) [3].”. He observed that the antibodies produced by a child to the first influenza A subtype infection continued to dominate There is an urgent need to better understand the immunologic responses to current licensed influenza vaccines in order to develop a more effective vaccine that does not rely on annual strain-matched boosters, provides broad protection, and is durable, i.e., a universal influenza vaccine.

Methods

Results

Discussion

Conclusion