Broad Antibody and Cellular Immune Response from a Phase 2 Clinical Trial with a Novel Multivalent Poxvirus-Based Respiratory Syncytial Virus Vaccine

Elke Jordan, Steven J. Lawrence, Thomas P.H. Meyer, Darja Schmidt, Stephanie Schultz, Jutta Mueller, Daria Stroukova, Brigitte Koenen, Robert Gruenert, Guenter Silbernagl, Sanja Vidojkovic, Liddy M. Chen, Heinz Weidenthaler, Nathaly Samy, Paul Chaplin

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective. Methods: This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule. Results: A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported. Conclusions: MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings. Clinical Trials Registration: NCT02873286

Original languageEnglish
Pages (from-to)1062-1072
Number of pages11
JournalJournal of Infectious Diseases
Volume223
Issue number6
DOIs
StatePublished - Mar 15 2021

Keywords

  • MVA-BN
  • RSV
  • antibody immune response
  • cellular immune response
  • poxvirus
  • recombinant RSV vaccine
  • respiratory syncytial virus
  • vaccine
  • viral vector

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