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Universal influenza vaccine based on conserved antigens provides long-term durability of immune responses and durable broad protection against diverse challenge virus strains in mice.
Lo, Chia-Yun; Misplon, Julia A; Li, Xing; Price, Graeme E; Ye, Zhiping; Epstein, Suzanne L.
  • Lo CY; Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Misplon JA; Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Li X; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Price GE; Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Ye Z; Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
  • Epstein SL; Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA. Electronic address: suzanne.epstein@fda.hhs.gov.
Vaccine ; 39(33): 4628-4640, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1292968
ABSTRACT
Current influenza vaccines rely on inducing antibody responses to the rapidly evolving hemagglutinin (HA) and neuraminidase (NA) proteins, and thus need to be strain-matched. However, predictions of strains that will circulate are imperfect, and manufacturing of new vaccines based on them takes months. As an alternative, universal influenza vaccines target highly conserved antigens. In proof of concept studies of universal vaccine candidates in animal models challenge is generally conducted only a short time after vaccination, but protective immunity lasting far longer is important for the intended public health impact. We address the challenge of providing long-term protection. We demonstrate here broad, powerful, and long-lasting immune protection for a promising universal vaccine candidate. A single intranasal dose of recombinant adenoviruses (rAd) expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) was used. Extending our previous studies of this type of vaccine, we show that antibody and T-cell responses persist for over a year without boosting, and that protection against challenge persists a year after vaccination and remains broad, covering both group 1 and 2 influenza A viruses. In addition, we extend the work to influenza B. Immunization with influenza B nucleoprotein (B/NP)-rAd also gives immune responses that last a year without boosting and protect against challenge with influenza B viruses of mismatched HA lineages. Despite host immunity to adenoviral antigens, effective readministration is possible a year after primary vaccination, as shown by successful immunization to a transgene product the animals had not seen before. Protection against challenge with divergent and highly pathogenic A/H7N9 virus was weaker but was enhanced by a second dose of vaccine. Thus, this mucosal vaccination to conserved influenza antigens confers very long-lasting immune protection in animals against a broad range of influenza A and B viruses.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Orthomyxoviridae Infections / Influenza A Virus, H7N9 Subtype Type of study: Prognostic study Topics: Vaccines Limits: Animals Language: English Journal: Vaccine Year: 2021 Document Type: Article Affiliation country: J.vaccine.2021.06.072

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Orthomyxoviridae Infections / Influenza A Virus, H7N9 Subtype Type of study: Prognostic study Topics: Vaccines Limits: Animals Language: English Journal: Vaccine Year: 2021 Document Type: Article Affiliation country: J.vaccine.2021.06.072