Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population

Abstract

Avian influenza viruses are currently one of the main threats to human health in the world. Although there are some screening reports of antibodies against these viruses in humans from Western countries, most of these types of studies are conducted in poultry and market workers of Asian populations. The presence of antibodies against avian influenza viruses was evaluated in an elderly European population. An experimental study was conducted, including pre- and post-vaccine serum samples obtained from 174 elderly people vaccinated with seasonal influenza vaccines of 2006–2007, 2008–2009, 2009–2010, and 2010–2011 Northern Hemisphere vaccine campaigns. The presence of antibodies against A/H5N1, A/H7N3, and A/H9N2 avian influenza viruses were tested by using haemaglutination inhibition assays. Globally, heterotypic antibodies were found before vaccination in 2.9% of individuals against A/H5N1, 1.2% against A/H7N3, and 25.9% against A/H9N2. These pre-vaccination antibodies were present at titers ≥1/40 in 1.1% of individuals against A/H5N1, in 1.1% against H7N3, and in 0.6% against the A/H9N2 subtype. One 76 year-old male showed pre-vaccine antibodies (Abs) against those three avian influenza viruses, and another three individuals presented Abs against two different viruses. Seasonal influenza vaccination induced a significant number of heterotypic seroconversions against A/H5N1 (14.4%) and A/H9N2 (10.9%) viruses, but only one seroconversion was observed against the A/H7N3 subtype. After vaccination, four individuals showed Abs titers ≥1/40 against those three avian viruses, and 55 individuals against both A/H5N1 and A/H9N2. Seasonal vaccination is able to induce some weak heterotypic responses to viruses of avian origin in elderly individuals with no previous exposure to them. However, this response did not accomplish the European Medicament Agency criteria for influenza vaccine efficacy. The results of this study show that seasonal vaccines induce a broad response of heterotypic antibodies against avian influenza viruses, albeit at a low level.

Antibodies against 1940s era a/H1N1 influenza strains a/Weiss/43 and a/FM/1/47 and heterotypic responses after seasonal vaccination of an elderly Spanish population

“…It is probable that these people currently have Abs against the 1940s era influenza viruses. On the other hand, current seasonal vaccines could help to increase the titre of pre-existing Abs by means of heterotypic responses, as has been shown in other studies against other influenza viruses [12]. These heterotypic responses are based on antigenic and genetic homology between the different types and subtypes of influenza viruses [13,14] and are extremely important for the design of universal influenza vaccines.…”

Heterotypic Neuraminidase Antibodies Against Different A(H1N1) Strains are Elicited after Seasonal Influenza Vaccination

“…Spain is one of the European countries with higher rates of vaccination, especially in those over 65 years of age [27], and contributes to a larger number of samples for epidemiological influenza surveillance conducted through Global Influenza Surveillance and Response System (GISRS) [28]. In addition, certain National Influenza Centers (NICs), such as the NIC Valladolid, have extensive experience in the annual collection of sera- and sero-epidemiological analysis, not only against subtypes and current strains but also against old influenza viruses [29,30].…”

Respuesta humoral específica y eficacia serológica de la vacuna frente al virus de la Gripe A (H1N1)

“…Los métodos empleados para su medida y los correlatos de seroprotección frente a la HA que deben utilizarse para evaluar la eficacia de las vacunas antigripales son objeto de debate actual. En el NIC de Valladolid se ha demostrado en trabajos recientes que las vacunas estacionales antigripales son capaces de producir respuestas humorales heterotípicas frente a virus no contenidos en su composición (100,141,142).…”

“…Las reacciones heterotípicas entre diferentes cepas de virus de la gripe, o incluso entre diferentes subtipos es frecuente. Existen trabajos que demuestran la existencia de respuestas cruzadas entre cepas diferentes de un mismo subtipo, tanto en la HA (47,100,105,141,142) como en la NA (155). La variabilidad de la HA es un logaritmo superior en magnitud a la de la NA (11), por lo que sería esperable, y parece confirmarse en este trabajo, que las respuestas heterotípicas de Acs frente a la NA pueden ser incluso más frecuentes.…”

“…En un trabajo previo del Dr. I. Sanz y colaboradores se demostró que un porcentaje moderado de la población ≥65 años tiene Acs heterotípicos a títulos protectores contra la cabeza globular de la HA de virus de la gripe no estacionales como el H5 y el H9 (141). Estos Acs estaban presentes como resultado de una respuesta cruzada con Acs frente a virus de gripe estacional, como H1 y H2, durante su vida.…”