Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy.

PLoS One. 2013;8(2):e57576.

De Marco MA, Porru S, Cordioli P, Cesana BM, Moreno A, Calzoletti L, Bonfanti L, Boni A, Di Carlo AS, Arici C, Carta A, Castrucci MR, Donatelli I, Tomao P, Peri VM, Di Trani L, Vonesch N.

Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. mariaalessandra.demarco@iss.it


BACKGROUND: Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus.

METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs.

CONCLUSION/SIGNIFICANCE: A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001) whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at early detection and control of SIVs with pandemic potential in humans.

PMID: 23469029



Viral exchange between human and animal populations is a crucial element in the origin of influenza pandemic strains, able to spread in an immunologically naïve human population. As in the pandemics of 1918, 1957 and 1968, caused by H1N1, H2N2 and H3N2 influenza A virus (IAV) antigenic subtypes, respectively, in the early third millennium the animal reservoir has played a key role in the origin and emergence of the 2009 H1N1 pandemic virus, turned out to be a quadruple reassortant containing IAV genes from pigs, birds and humans.

In this epidemiological context, pigs are an important intermediate host for interspecies reassortment events, possibly occurring in pig tracheal epithelial cells during simultaneous infection of both avian and mammalian influenza A viruses. In addition, it is well known the ability of pigs to adapt avian viruses to mammals, enabling the virus to cross the species barrier.

The study by De Marco et al. was planned to investigate the health risk of occupational exposure to swine influenza viruses (SIVs) isolated from farms of the Lombardia Region, a densely populated pig area characterised by an endemic SIV circulation. Between 2008 and 2010 human sera were collected from swine workers (SWs) and control subjects (Cs) unexposed to pigs. Sera were tested for antibodies against SIVs circulating in the farms under study and representative of the Eurasian avian-like H1N1 and human-like H3N2 and H1N2 lineages (swH1N1, swH3N2 and swH1N2, respectively). SIVs were isolated from nasal swabs taken from pigs with respiratory symptoms or from lungs of pigs submitted to the necropsy lab for routine diagnostic examinations (Figure 1).

Maria Alessandra De Marco-1

The present occupational study is unique in that its time frame included the complete periods of onset and global spread of the H1N1 2009 influenza pandemic (H1N1pdm), thus giving the opportunity to compare the immune response in the SWs and Cs study groups before and after the pandemic peak.

Results of the study provide serologic evidence of swH1N1 transmission from pigs to Italian swine workers, and suggest that anti-swH1N1 antibodies have induced cross-protective immunity against the H1N1pdm virus.

These findings, resulted from an integrated medical-veterinary surveillance approach, aim to develop new strategies for prevention and protection of workers and, in addition, open up perspectives on potential applications of heterologous cross-protective immunity elicited by human and animal influenza A viruses.



Maria Alessandra De Marco, DVM, PhD

Laboratory of Genetics

Istituto Superiore per la Protezione e la Ricerca Ambientale (ISPRA)

(Institute for Environmental Protection and Research)

Via Ca’ Fornacetta 9

40064 Ozzano Emilia (Bologna), Italy

Tel: +390516512205

Fax: +39051796628

Email: mariaalessandra.demarco@isprambiente.it

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