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Detection of neuraminidase inhibitor-resistant influenza A (H1N1)pdm09 viruses obtained from influenza surveillance in Indonesia.

ABSTRACT: Background:Influenza antiviral resistance has been shown to occur in many countries and is commonly found in influenza A(H1N1)pdm09 and A(H3N2). In this study, we monitored and investigated the neuraminidase inhibitor resistance of influenza A(H1N1)pdm09 viruses through the influenza surveillance system in Indonesia. Methods:A total of 4752 clinical specimens were collected from patients with influenza-like illness and severe acute respiratory infection during the year 2016. An allelic discrimination assay was conducted by a single base substitution or a single-nucleotide polymorphism that is specific to the H275 wild-type and Y275 mutant. Sequencing was performed to confirm the H275Y mutations, and we analysed the phylogenetic relationship. Results:The first occurrence of oseltamivir-resistant influenza A(H1N1)pdm09 was observed in the samples from the influenza-like illness surveillance. Two H275Y oseltamivir-resistant viruses (0.74%) out of 272 influenza A(H1N1)pdm09 positives were found. Both of them were collected from untreated patients. Conclusion:The number of oseltamivir-resistant influenza A(H1N1)pdm09 viruses in Indonesia is very low. However, it is necessary to continue with active surveillance for oseltamivir resistance in severe and mild cases.

SUBMITTER: Pawestri HA

PROVIDER: S-EPMC6295675 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza virus infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralizing anti-HA antibodies against HA antigenic variants. Here, we systematically characterized the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950 and 2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4 to 12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations. IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analyzed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950 and 2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. A total of 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy.

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Detection of neuraminidase inhibitor-resistant influenza A (H1N1)pdm09 viruses obtained from influenza surveillance in Indonesia.

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