Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans

Abstract

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans

Dose Effects of Recombinant Adenovirus Immunization in Rodents

“…However, as seen in this study, the immune correlates may not be predictive of protection against infectious diseases. A recent study that examined the response to repetitive vaccination in humans found that there was a significant reduction in hemagglutination inhibition titers after the second immunization with an identical vaccine [47]. This study may shed light on why a high dose and repeat vaccinations do not always induce typical anamnestic responses.…”

Human Influenza Epidemiology

“…An example of this is shown in Figure 1A, based on a serological study done in Hong Kong in 2009 (Wu et al 2010b). However, some technical issues must be addressed, including uncertainty over the proportion of infected individuals who develop antibody at or above a certain titer ( particularly among those with subclinical infections), the delays in appearance of antibody, waning in antibody titers over the longer term, potential cross-reactions due to infections with other strains, and con- fusion of changes in antibody titer following vaccination versus infection (Chen et al 2018;Khurana et al 2019). Incidence can also be measured in closed settings such as schools and households, and outbreak investigations or transmission studies can provide valuable data on infections and illnesses.…”

Respuesta inmune humoral inducida por la vacuna influenza en niños con diagnóstico de leucemia linfoblástica aguda

“…Respecto a la vacunación previa, una mayor proporción de niños sanos se vacunaba por primera vez comparado con los niños con LLA, sin alcanzar una diferencia significativa. Este antecedente concuerda con recientes evidencias respecto a que la vacuna recibida en forma repetida podría disminuir la efectividad de subsiguientes dosis de esta vacuna, reduciendo la afinidad de los anticuerpos, entre otros mecanismos 36 . Los trabajos que incluyen grupos control con niños sanos como en este estudio, también muestran una respuesta superior a la observada en niños con LLA, pero sólo en un reporte esta diferencia fue estadísticamente significativa 20,21 .…”