Safety and Immunogenicity of mRNA-LNP COVID-19 Vaccine CVnCoV in Latin American Adults; A Phase 2 Randomized Study

Abstract

Background: The COVID-19 vaccine candidate CVnCoV comprises sequence-optimized mRNA encoding SARS-CoV-2 S-protein encapsulated in lipid nanoparticles. In this phase 2a study, we assessed reactogenicity and immunogenicity of two or three doses in younger and older adults.

Methods: Younger (18–60 years) and older (> 60 years) adults were enrolled in two sites in Panama and Peru to receive either 6 or 12 µg doses of CVnCoV or licensed control vaccines 28 days apart; subsets received a 12 µg booster dose on Day 57 or Day 180. Solicited adverse events (AE) were reported for 7 days and unsolicited AEs for four weeks after each vaccination, and serious AEs (SAE) throughout the study. Humoral immunogenicity was measured as neutralizing and receptor binding domain (RBD) IgG antibodies and cellular immunogenicity was assessed as CD4+/CD8+ T cell responses.

Results: A total of 668 participants were vaccinated (332 aged 18–60 years and 336 aged > 60 years) including 75 who received homologous booster doses. Vaccination was well tolerated with no vaccine-related SAEs. Solicited and unsolicited AEs were mainly mild to moderate and resolved spontaneously. Both age groups demonstrated robust immune responses as neutralizing antibodies or RBD IgG, after two doses, with lower titers in the older age group than the younger adults. Neither group achieved levels observed in human convalescent sera (HCS), but did equal or surpass HCS levels following homologous booster doses. Following CVnCoV vaccination, robust SARS-CoV-2 S-protein-specific CD4+ T-cell responses were observed in both age groups with CD8+ T-cell responses in some individuals, consistent with observations in convalescing COVID-19 patients after natural infection.

Conclusions: We confirmed that two 12 µg doses of CVnCoV had an acceptable safety profile, and induced robust immune responses. Marked humoral immune responses to homologous boosters suggest two doses had induced immune memory.

Note:
Funding: This trial was funded by the German Federal Ministry of Education and Research (grant 01KI20703), and CureVac AG.

Declaration of Interests: Sandra Lazzaro, Gianliuca Quinitini, Barkha Srivastava and Olaf-Oliver Wolz are employees of CureVac; Marina Gonzalez, Sarah-Katharina Kays, Philipp Mann, Lidia Oostvogels, Dominik Vahrenhorst and Philipp von Eisenhart-Rotheare employees of CureVac and have stock options. Carlos R. Celis, Rubelio Cornejo, Lucie Ecker,Ana I Gil, Claudio F. Lanata and Geert Leroux-Roels, report receiving funding through their institutions for the study, Helga Junker, Sven D. Koch and Geert Leroux-Roelsreceived consulting feesfrom CureVac. Elaine Aranguren, Diego Carrido, Rodrigo DeAntonio, Diegi Garrido,Morgan Hess-Holtz and Xavier Sáez-Llorens report no competing interests.

Ethics Approval Statement: The protocol was approved by the appropriate institutional and national ethics committees - Panama, approval 08.08.2020: CNBI (National Bioethics Committee of Investigation Republic of Panama) Clayton Ciudad del Saber Edif.205, Panama; Peru, approval 11.08.2020: CNTEI-COVID19 Temporary National Research Ethics Committee for the Evaluation and Ethical Supervision of Clinical Trials for COVID-19. The trial is being performed according to ICH E6 and Good Clinical Practice guidelines. All participants provided written informed consent at enrollment. The study is being overseen by an internal Safety Review Committee (iSRC) and an independent Data Safety Monitoring Board (DSMB) composed of external experts.

Trial Registration: Registered at ClinicalTrials.gov NCT04515147

Keywords: COVID-19, vaccine, mRNA, clinical trial