tetano
Editor, Senior Moderator
NPJ Vaccines
. 2024 Oct 7;9(1):183.
doi: 10.1038/s41541-024-00980-3. Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines
Teresa Hauguel[SUP] #[/SUP][SUP] 1 [/SUP], Amy Sharma[SUP] #[/SUP][SUP] 2 [/SUP], Emily Mastrocola[SUP] 1 [/SUP], Susan Lowry[SUP] 1 [/SUP], Mohan S Maddur[SUP] 1 [/SUP], Cheng Hui Hu[SUP] 1 [/SUP], Swati Rajput[SUP] 1 [/SUP], Allison Vitsky[SUP] 3 [/SUP], Shambhunath Choudhary[SUP] 2 [/SUP], Balasubramanian Manickam[SUP] 4 [/SUP], Ivna De Souza[SUP] 1 [/SUP], Yana Chervona[SUP] 2 [/SUP], Raquel Munoz Moreno[SUP] 1 [/SUP], Charisse Abdon[SUP] 1 [/SUP], Larissa Falcao[SUP] 1 [/SUP], Kristin Tompkins[SUP] 1 [/SUP], Deanne Illenberger[SUP] 1 [/SUP], Rachel Smith[SUP] 1 [/SUP], Fanyu Meng[SUP] 1 [/SUP], Shuai Shi[SUP] 1 [/SUP], Kari Sweeney Efferen[SUP] 1 [/SUP], Victoria Markiewicz[SUP] 4 [/SUP], Cinthia Umemoto[SUP] 1 [/SUP], Jianfang Hu[SUP] 5 [/SUP], Wei Chen[SUP] 1 [/SUP], Ingrid Scully[SUP] 1 [/SUP], Cynthia M Rohde[SUP] 2 [/SUP], Annaliesa S Anderson[SUP] 1 [/SUP], Pirada Suphaphiphat Allen[SUP] 6 [/SUP]
Affiliations
Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4[SUP]+[/SUP] T cell responses, and HA-specific CD8[SUP]+[/SUP] T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ[SUP]+[/SUP] CD4[SUP]+[/SUP] T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.
. 2024 Oct 7;9(1):183.
doi: 10.1038/s41541-024-00980-3. Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines
Teresa Hauguel[SUP] #[/SUP][SUP] 1 [/SUP], Amy Sharma[SUP] #[/SUP][SUP] 2 [/SUP], Emily Mastrocola[SUP] 1 [/SUP], Susan Lowry[SUP] 1 [/SUP], Mohan S Maddur[SUP] 1 [/SUP], Cheng Hui Hu[SUP] 1 [/SUP], Swati Rajput[SUP] 1 [/SUP], Allison Vitsky[SUP] 3 [/SUP], Shambhunath Choudhary[SUP] 2 [/SUP], Balasubramanian Manickam[SUP] 4 [/SUP], Ivna De Souza[SUP] 1 [/SUP], Yana Chervona[SUP] 2 [/SUP], Raquel Munoz Moreno[SUP] 1 [/SUP], Charisse Abdon[SUP] 1 [/SUP], Larissa Falcao[SUP] 1 [/SUP], Kristin Tompkins[SUP] 1 [/SUP], Deanne Illenberger[SUP] 1 [/SUP], Rachel Smith[SUP] 1 [/SUP], Fanyu Meng[SUP] 1 [/SUP], Shuai Shi[SUP] 1 [/SUP], Kari Sweeney Efferen[SUP] 1 [/SUP], Victoria Markiewicz[SUP] 4 [/SUP], Cinthia Umemoto[SUP] 1 [/SUP], Jianfang Hu[SUP] 5 [/SUP], Wei Chen[SUP] 1 [/SUP], Ingrid Scully[SUP] 1 [/SUP], Cynthia M Rohde[SUP] 2 [/SUP], Annaliesa S Anderson[SUP] 1 [/SUP], Pirada Suphaphiphat Allen[SUP] 6 [/SUP]
Affiliations
- PMID: 39375384
- DOI: 10.1038/s41541-024-00980-3
Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4[SUP]+[/SUP] T cell responses, and HA-specific CD8[SUP]+[/SUP] T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ[SUP]+[/SUP] CD4[SUP]+[/SUP] T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.