Sex: U
Vaccine: FLU4
Symptoms: Antibody test positive, Gene sequencing, H3N2 influenza, Influenza A virus test positive, Polymerase chain reaction positive
Clinical narrative: Suspected vaccination failure; influenza A(H3N2); acute respiratory illness; This case was reported in a literature article and described the occurrence of suspected vaccination failure in a adult patient who received Flu Seasonal QIV Dresden (Flu Seasonal QIV Dresden) for prophylaxis.   On an unknown date, the patient received Flu Seasonal QIV Dresden at an unknown dose. On an unknown date, less than a year after receiving Flu Seasonal QIV Dresden, the patient experienced vaccination failure (serious criteria hospitalization and GSK medically significant), h3n2 influenza (serious criteria hospitalization) and respiratory disorder (serious criteria hospitalization). On an unknown date, the outcome of the vaccination failure, h3n2 influenza and respiratory disorder were unknown.   It was unknown if the reporter considered the vaccination failure, h3n2 influenza and respiratory disorder to be related to Flu Seasonal QIV Dresden.  Additional details were reported as follows: This case was reported in a literature article and described the suspected vaccination failure in a patient aged between 22 and 63 years of unspecified gender, who was vaccinated with unspecified quadrivalent influenza vaccine (manufacturer GlaxoSmithKline) for prophylaxis.   The patient was a part of the study that aimed was to compare antibody titers against both circulating influenza A (H3N2) strains and egg-adapted influenza A (H3N2) strains in acute specimens from individuals with and those without influenza virus infection in the 2017-2018 season. During the severe 2017-2018 influenza season, a study of the effectiveness of influenza vaccine among inpatients with acute respiratory illness as part of the Centers for Disease Control and Prevention (CDC) sponsored Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) was performed. No information on patient's medical history, family history, concurrent condition or concomitant medication was provided. On unspecified date, during 2017-2018 influenza season, the patient received unspecified quadrivalent influenza vaccine (administration route and site unspecified; dosage unknown; batch number not provided). The age at vaccination was not provided. [In this study, there were 18 individuals who had been vaccinated, and the specific influenza vaccine they received could be confirmed for 15. All 15 individuals with confirmed vaccine product information received vaccines containing inactivated egg grown virus; 10 received quadrivalent standard dose vaccines (9 vaccines were produced by GlaxoSmithKline, and 1 was produced by Seqirus), 3 received trivalent high dose vaccines (produced by Sanofi Pasteur), 1 received trivalent adjuvanted vaccine (produced by Seqirus), and 1 received trivalent unadjuvanted vaccine (produced by Seqirus)]. On an unspecified date, during 2017-2018 influenza season, between 27 November 2017 and 31 January 2018, an unknown period after the vaccination, the patient developed acute respiratory illness and subsequently hospitalized. The patient was enrolled less than or equal to 10 days after illness onset during active influenza virus circulation. The patient's throat and nasal swab specimens were collected shortly for influenza virus identification by reverse transcription polymerase chain reaction (RT-PCR) analysis. The patient was found influenza A(H3N2) Positive The patient's antibody titers were also measured with neuraminidase-inhibition (NAI) and Microneutralization (MN) assays was determined. The microneutralization (MN) egg propagated A/HongKong/4801/2014 (HK-egg) antibody titer was found 20, MN MDCK-SIAT1 propagated A/HongKong/4801/2014 (HK) antibody titer was found 20, MN MDCK-SIAT1 propagated A/Washington/16/2017 (WA) antibody titer was found 10, MN MDCK-SIAT1 propagated A/Singapore/Infimh-16-0019/2016 (SG) antibody titer was 10, MN MDCK-SIAT1 propagated A/Maryland/53/2017 (MD) antibody titer was found 10, MN MDCK-SIAT1 propagated A/Wisconsin/327/2017 (WI) antibody titer was found 10, neuraminidase-inhibition (NAI) MDCK-SIAT1 propagated A/HongKong/4801/2014 (HK) antibody titer was found 80 and NAI MDCK-SIAT1 propagated A/Singapore/Infimh-16-0019/2016 (SG) antibody titer was found 160 in patient. The genetic characterization of Influenza A(H3N2) virus strains circulating in patient sample was also determined (results not provided). This case has been considered as suspected vaccination failure being the time to onset was unknown. This case has been considered as serious due to suspected vaccination failure and hospitalization. Treatment was unknown. The outcome of the event was not reported. The author did not comment on the relationship between the event of influenza A (H3N2) infection and unspecified Quadrivalent influenza vaccine. However, the authors stated, "This analysis of specimens from adults hospitalized with influenza A(H3N2) virus infection during the 2017-2018 influenza season demonstrated an antibody response specific to egg-adapted strains that was significantly higher among vaccinated individuals. In our study sample, this suggests that the antibody responses to vaccination in this population are highly specific to the egg-adapted strain, with little cross-reactivity to the circulating virus. Additionally, antibody titers against cell grown influenza A/HongKong/4801/2014(H3N2) virus were similar to those in unvaccinated individuals. In this study sample, this suggests that the antibody responses to vaccination in this population are highly specific to the egg adapted strain, with little cross-reactivity to the circulating virus. In this study, antibody against the neuraminidase of influenza A/HongKong/4801/2014 virus and influenza A/Singapore/INFIMH-16-0019/2016 virus was not associated with protection against infection. Although neuraminidase content was not standardized in influenza vaccines, it was observed that anti neuraminidase antibody titers were higher among vaccinated individuals, suggesting that some of the existing anti neuraminidase antibody in this population resulted from vaccination. The serum specimens in this study were collected at a single time point early during acute illness." The authors concluded, "The conclusions were limited by the inclusion of a small number of specimens from a single hospital. Because the severity of the 2017-2018 epidemic was evident early in the season, it was prioritized rapid serologic testing of the specimens that were available to date during the first half of the season. These 2 factors may limit the broad generalizability of the results; however, the influenza viruses that circulated locally overall and during the analysis period were similar to those that predominated nationwide during the same season. The small sample size also precluded the ability to perform additional subanalyses, to assess whether results might vary within specific age groups or by history of prior vaccination. In one sense, the 2017-2018 influenza vaccine appears to have worked as intended: vaccinated individuals had high antibody titers against the influenza virus strain included in the vaccine. The study adds to the evidence that egg adaptations in the 2017-2018 influenza vaccine strain elicited antibodies to epitopes not conserved in circulating strains. The degree to which this contributed to the marked severity of the 2017- 2018 season remains to be determined. Several vaccine products have been introduced into the vaccine market that are produced in cells and do not have the same emergent egg adaptations seen in recent influenza A(H3N2) vaccine strains. At this time, evidence for the effectiveness of these vaccines relative to those produced in eggs is limited because few head to head trials have been performed. Early data suggest that cell based vaccines have somewhat improved protection in clinical trials and in the community. Unfortunately, these vaccines are still dependent on selecting viruses that are close antigenic matches to those that will circulate and are subject to the limitations of annual strain selection time lines. This underscores the need for the development of the next generation of influenza vaccines that provide better, broader, and longer lasting protection." This is 1 of the 4 valid cases reported in the same literature article.      Lab Comments: On an unspecified date, during 2017-2018 influenza season, between 27 November 2017 and 31 January 2018, the lab test were performed. The patient's antibody titers were also measured with neuraminidase-inhibition (NAI) and Microneutralization (MN) assays was determined. The microneutralization (MN) egg propagated A/HongKong/4801/2014 (HK-egg) antibody titer was found 20, MN MDCK-SIAT1 propagated A/HongKong/4801/2014 (HK) antibody titer was found 20, MN MDCK-SIAT1 propagated A/Washington/16/2017 (WA) antibody titer was found 10, MN MDCK-SIAT1 propagated A/Singapore/Infimh-16-0019/2016 (SG) antibody titer was 10, MN MDCK-SIAT1 propagated A/Maryland/53/2017 (MD) antibody titer was found 10, MN MDCK-SIAT1 propagated A/Wisconsin/327/2017 (WI) antibody titer was found 10, neuraminidase-inhibition (NAI) MDCK-SIAT1 propagated A/HongKong/4801/2014 (HK) antibody titer was found  80 and NAI MDCK-SIAT1 propagated A/Singapore/Infimh-16-0019/2016 (SG) antibody titer was found 160 in patient. The genetic characterization of Influenza A(H3N2) virus strains circulating in patient sample was also determined (results not provided).