Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

Abstract

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults. The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Epidemiology of influenza B infection in the state of Rio Grande do Sul, Brazil, from 2003 to 2019

“…Both IBV Victoria and Yamagata were recently reported to co‐circulate in many regions over the globe, therefore constant surveillance is important when choosing a vaccine. In this study, a low rate of vaccination was observed among IBV‐infected patients; also, vaccinal mismatch should not be disregarded as an explanation for the fact that approximately 25% of the hospitalized patients with SARI had received the flu vaccine and, still, were infected with IBV—probably of a lineage not present in the annual vaccine composition 26 . The estimated rate of vaccinal mismatch reported in previous studies can be >91% in Brazil and 52% in South America 26 …”

“…In this study, a low rate of vaccination was observed among IBV-infected patients; also, vaccinal mismatch should not be disregarded as an explanation for the fact that approximately 25% of the hospitalized patients with SARI had received the flu vaccine and, still, were infected with IBV-probably of a lineage not present in the annual vaccine composition. 26 The estimated rate of vaccinal mismatch reported in previous studies can be >91% in Brazil and 52% in South America. 26 The main limitation of this study was the lack of data, which occurred because the notification systems changed along the period; therefore, some data was only available for a limited number of cases, and some variables had missing values.…”

Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older

“…This is not unexpected given the tendency for older adults to have high baseline HI antibody titers, arising from either natural exposure to influenza or previous vaccinations, which have been reported to reduce antibody responses to subsequent seasonal influenza vaccination [18–20]. In populations with high prevaccination SPRs, such as those seen in our study, it is difficult to demonstrate an improved immune response based on SCRs alone [21]. In addition, the immune responses to influenza vaccines are often less robust in older adults owing to immunosenescence [22–24].…”

Immunogenicity of Split Inactivated Quadrivalent Influenza Vaccine in Adults with Obesity in the 2017/2018 Season

“…The reason for this may be a sharp decrease in anti-HI titers against vaccine strains after 12 months following influenza vaccination, which has been observed in people with obesity [ 6 ]. The post-vaccination GMT were also lower in studied subjects compared to the general adult population [ 26 28 , 32 34 ]. However, it cannot be excluded that differences in GMT levels described in the literature likely reflect, at least in part, the inter-laboratory discrepancies in titer measurements.…”