Sex: M
Vaccine: FLUX
Symptoms: Cardiac arrest, Death
Clinical narrative: Initial unsolicited report received from the literature on 18-Sep-2017. This case is linked with: 2017SA173133. Verbatim of the article: This is the second phase 1 study of a respiratory syncytial virus (RSV) vaccine containing RSV fusion protein (sF) adjuvanted with glucopyranosyl lipid A (GLA) in a squalene-based 2% stable emulsion (GLA-SE). In this randomized, double blind study, 261 subjects aged _60 years received inactivated influenza vaccine (IIV), a vaccine containing 120 _g sF with escalating doses of GLA (1, 2.5, or 5 _g) in SE, or a vaccine containing 80 _g sF with 2.5 _g GLA in SE. Subjects receiving 120 _g sF with 2.5 or 5 _g GLA were also randomized to receive IIV or placebo. Immunity to RSV was assessed by detection of microneutralizing, anti-F immunoglobulin G, and palivizumab-competitive antibodies and F-specific gamma interferon enzyme linked immunosorbent spot assay T-cell responses. Higher adjuvant doses increased injection site discomfort, but at the highest dose, the reactogenicity was similar to that of IIV. Significant humoral and cellular immune responses were observed. The 120 _g sF plus 5.0 _g GLA formulation resulted in the highest responses in all subjects and in older subjects. These results confirm previous observations of vaccine tolerability, safety, and immunogenicity and were used to select the 120 _g sF plus 5.0g GLA formulation for phase 2 evaluation. Ethics statement. The study was carried out in accordance with the Declaration and good clinical practice guidelines. The study protocol and amendments and the subject informed consent document were approved by the Independent Review Board and the Review Board. All subjects provided written informed consent. Study design. In this phase 1b, double-blind, controlled, adjuvant-escalation (1.0, 2.5, and 5 _g of GLA) study conducted in adults _60 years of age, 264 subjects (healthy subjects or subjects with stable chronic illnesses) were to be enrolled at 5 centers in 2015. They were randomized by cohort, as described, using an Internet-based interactive response system. Subjects received 1 vaccine in cohorts 1 and 4. For cohorts 2 and 3, in which the subjects received an RSV vaccine and either IIV or placebo to assess the safety and immunogenicity of concurrently administered IIV and RSV vaccines, the vaccines were randomly assigned to be administered in the right or the left arm. The dose of 80 _g of sF plus 2.5 _g of GLA was included to bridge to phase 1a study data. In a preplanned interim analysis, some investigators were made unblind to the treatments after the subjects had completed 90 days of safety follow-up, but site staff and subjects remained blind to the treatments until the end of the study (day 361).Subjects. Subjects were required to be _60 years of age, to be not institutionalized or homebound, to weigh _40.9 kg, and to have met a gender-specific hemoglobin requirement. Major exclusions included an unstable medical condition or a recent change in therapy, receipt of influenza vaccine within the previous 60 days, receipt of products that could include exogenous antibodies, clinically significant abnormalities in screening tests, viral hepatitis, a history of or current autoimmune disorder other than hypothyroidism, immunosuppression, a body mass index of _40 kg/m2, or the taking of medications or the existence of conditions that could cause injection site bleeding. Study vaccines. sF in the postfusion conformation derived and modified from the sequence of an RSV A strain was expressed in a hamster ovary cell line. GLA-SE was provided by and licensed from Corporation pursuant to an existing agreement. RSV sF was from the same lot used in the phase 1a study; GLA-SE was remanufactured to use non-egg-derived phosphatidylcholine. FLUZONE was purchased commercially and provided to the study sites. To prepare vaccine on-site, lyophilized RSV sF was reconstituted with sterile water and combined with liquid diluent, GLA-SE, and SE in a mixing vial to reach the concentrations of sF, GLA, and SE specified for each cohort. For all vaccines, a single 0.5-ml dose was drawn into a covered syringe to maintain the blind and administered into the deltoid muscle with a needle of the gauge and length described in previously published guidelines. Study assessments. Specified solicited symptoms were recorded using a diary card between days 1 (dosing) and 7; AEs were recorded between day 1 and the day 29 visit; and serious AEs, new-onset chronic diseases, and AESIs, including events of potential autoimmune etiology, were recorded from days 1 to 361. Visits occurred on (approximately) days 1, 8, 29, 61, 91, 181, 271, and 361. Subjects were contacted by telephone at least monthly for safety follow-up. Toxicity grading was generally consistent with that on a standard table. This case involves 79-year-old male patient, who was vaccinated with a dose of INFLUENZA VACCINE (batch number, expiry date, dose, dose in series site and route of administration were not reported) on an unknown date. The patient's medical history was not reported. Patient concomitantly received placebo as part of trial procedure. On an unknown date, 320 days following the vaccination patient had cardiac arrest. Other laboratory test and corrective treatment were not reported. On an unknown date, patient died. It was not reported whether autopsy was performed or not. As per the reporter relationship to study dosing was reported as not related. List of documents held by sender: none. Sender's Comments: This case concerns a 79 year old male who died due to cardiac arrest on 320 days post vaccination with Inactivated Influenza vaccine (MFR unknown). Time to onset is too long to be compatible with the role of vaccine. More details regarding patient's medical history (concurrent illness), previous vaccination history, time of death and autopsy report are needed for complete assessment of the case. Based on the available information no conclusion can be drawn. Reported Cause(s) of Death: cardiac arrest.