Influenza B Lineages Have More in Common Than Meets the Eye. Trivalent Influenza Vaccines Trigger Heterotypic Antibodies Against Both Influenza B Viruses

Abstract

Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.

Differential Cross-Protective Immunity is Elicited by Infection with Contemporary Influenza B Lineage Viruses

“…During a naturally acquired influenza infection, antibodies are primarily elicited against the major surface glycoproteins, HA and NA, and are essential in protecting from repeat infections (22,23). HA-specific antibodies are necessary for viral neutralization and a subset of these antibodies bind moderately conserved epitopes near the globular head and stem, allowing for cross-reactive responses between the FLUAV subtypes and FLUBV lineages (5,20,(24)(25)(26). In addition, NA-specific antibodies have recently been highlighted for playing a role in crossprotective influenza immunity (27)(28)(29)(30)(31)(32).…”

“…The co-circulation of influenza A and B viruses (FLUAV and FLUBV) during seasonal epidemics causes a significant disease and economic burden (1–3). Additionally, it complicates vaccine development and efficacy due to the expansion from bi- and tri-valent formulations to quadrivalent formulations to broaden the breadth of protection from seasonal vaccines (4, 5). Although understudied compared to its FLUAV counterpart, FLUBV plays an essential role in the epidemiology of seasonal infections, accounting for approximately 25% of influenza cases and hospitalizations each season and circulates as the predominant influenza type in one of every seven seasons (3, 4, 6–8).…”

“…The co-circulation of influenza A and B viruses (FLUAV and FLUBV) during seasonal epidemics causes a significant disease and economic burden (1-3). Additionally, it complicates vaccine development and efficacy due to the expansion from bi-and tri-valent formulations to quadrivalent formulations to broaden the breadth of protection from seasonal vaccines (4,5).…”

Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines

“…However, both epidemiological and serological studies support the hypothesis that cattle are the natural reservoir. To date there is no direct evidence of IDV disease in humans, but antibodies against IDV have been detected, underlining the potential ability of this virus to infect and elicit an immune response in humans and especially in people working with animals and/or exposed to cattle [ 15 , 16 , 17 , 18 , 19 , 20 ].…”