Controversias sobre vacunas en España, una oportunidad para la vacunología social Translated title: Controversies over vaccines in Spain, a chance for social vaccinology

The sleep disorder narcolepsy is linked to the HLA-DQB1*0602 haplotype and dysregulation of the hypocretin ligand-hypocretin receptor pathway. Narcolepsy was associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic. In contrast, very few cases were reported after Focetria vaccination (a differently manufactured adjuvanted influenza pandemic vaccine). We hypothesized that differences between these vaccines (which are derived from inactivated influenza viral proteins) explain the association of narcolepsy with Pandemrix-vaccinated subjects. A mimic peptide was identified from a surface-exposed region of influenza nucleoprotein A that shared protein residues in common with a fragment of the first extracellular domain of hypocretin receptor 2. A significant proportion of sera from HLA-DQB1*0602 haplotype-positive narcoleptic Finnish patients with a history of Pandemrix vaccination (vaccine-associated narcolepsy) contained antibodies to hypocretin receptor 2 compared to sera from nonnarcoleptic individuals with either 2009 A(H1N1) pandemic influenza infection or history of Focetria vaccination. Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2, which was demonstrated by competitive binding using 21-mer peptide (containing the identified nucleoprotein mimic) and 55-mer recombinant peptide (first extracellular domain of hypocretin receptor 2) on cell lines expressing human hypocretin receptor 2. Mass spectrometry indicated that relative to Pandemrix, Focetria contained 72.7% less influenza nucleoprotein. In accord, no durable antibody responses to nucleoprotein were detected in sera from Focetria-vaccinated nonnarcoleptic subjects. Thus, differences in vaccine nucleoprotein content and respective immune response may explain the narcolepsy association with Pandemrix.

Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States.

Vaccines save millions of lives every year. They are one of the safest and most effective public health interventions in keeping populations healthy while bringing numerous social and economic benefits. Vaccines play an important role in ensuring that children, regardless of where they live, can have a healthy start to life. New financing mechanisms that allow poorer countries to gain access to vaccines faster than ever mean additional deaths and disabilities are projected to be saved during the Decade of Vaccines (2011-2020). Trust in vaccines and in the health system is an important element of public health programs that aim to deliver life-saving vaccines. Indeed, understanding the contributors and threats to trust is essential to explaining vaccine acceptance, particularly as they vary across epidemiologic conditions, specific vaccines and cultural and sociopolitical settings. Greater efforts to communicate the benefits and risks of vaccines and address issues with evidence-based information will help improve and sustain public trust in vaccines and health systems worldwide. Measuring and monitoring trust levels and focusing on deliberate efforts to build trust in vaccines are important steps to reducing vaccine confidence gaps when they occur.