Moderately Low Effectiveness of the Influenza Quadrivalent Vaccine: Potential Mismatch between Circulating Strains and Vaccine Strains

Abstract

The annual seasonal influenza vaccination is the most effective way of preventing influenza illness and hospitalization. However, the effectiveness of influenza vaccines has always been controversial. Therefore, we investigated the ability of the quadrivalent influenza vaccine to induce effective protection. Here we report strain-specific influenza vaccine effectiveness (VE) against laboratory-confirmed influenza cases during the 2019/2020 season, characterized by the co-circulation of four different influenza strains. During 2019–2020, 778 influenza-like illness (ILI) samples were collected from 302 (39%) vaccinated ILI patients and 476 (61%) unvaccinated ILI patients in Riyadh, Saudi Arabia. VE was found to be 28% and 22% for influenza A and B, respectively. VE for preventing A(H3N2) and A(H1N1)pdm09 illness was 37.4% (95% CI: 43.7–54.3) and 39.2% (95% CI: 21.1–28.9), respectively. The VE for preventing influenza B Victoria lineage illness was 71.7% (95% CI: −0.9–3), while the VE for the Yamagata lineage could not be estimated due to the limited number of positive cases. The overall vaccine effectiveness was moderately low at 39.7%. Phylogenetic analysis revealed that most of the Flu A genotypes in our dataset clustered together, indicating their close genetic relatedness. In the post-COVID-19 pandemic, flu B-positive cases have reached three-quarters of the total number of influenza-positive cases, indicating a nationwide flu B surge. The reasons for this phenomenon, if related to the quadrivalent flu VE, need to be explored. Annual monitoring and genetic characterization of circulating influenza viruses are important to support Influenza surveillance systems and to improve influenza vaccine effectiveness.

Sustained vaccine exposure elicits more rapid, consistent, and broad humoral immune responses to multivalent influenza vaccines

“…Over the past decade, seasonal influenza vaccines have had an average effectiveness of just 40% [2] , and influenza infection rates have quickly returned to pre-COVID-19 pandemic levels [3] . While typical seasonal influenza vaccines comprise the 3-4 subtypes predicted to be the most prevalent each year, the challenges with selecting the correct viruses to include each year are compounded by the dramatic variability in effectiveness against each influenza virus in the vaccine [4][5][6][7] . Additionally, the threat of interspecies transmission of highly pathogenic strains such as H5N1 avian influenza remains at the forefront of our disease monitoring as growing population density and large-scale agriculture increase the opportunities for viral mutation and zoonotic spillover [8][9][10] .…”

Nucleoprotein as a Promising Antigen for Broadly Protective Influenza Vaccines

“…However, this property of viral surface proteins also makes them a major target for viral evolution toward host defense evasion and increases their susceptibility to escape mutations [ 6 ]. This variability of surface antigens requires an almost annual update of influenza vaccine strain compositions and often leads to reduced vaccine effectiveness when there is an antigenic mismatch between circulating and vaccine strains [ 7 , 8 ]. Therefore, the development of influenza vaccines with broader and more durable protection against seasonal and potentially pandemic influenza strains is of high priority [ 9 ].…”