Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

Masoud Solaymani Dodaran; Seyed Reza Banihashemi; Ali Es-Haghi; Mohammad Hossein Fallah Mehrabadi; Mojtaba Nofeli; Ali Rezaei Mokarram; Ladan Mokhberalsafa; Fariba Sadeghi; Alireza Ranjbar; Akram Ansarifar; Arash Mohazzab; Seyed Amin Setarehdan; Fahimeh Bagheri Amiri; Vahideh Mohseni; Monireh Hajimoradi; Neda Ghahremanzadeh; Seyed Hossein Razzaz; Safdar Masoomi; Maryam Taghdiri; Mohsen Bagheri; Mohsen Lofti; Akbar Khorasani; Masoud Ghader; Shiva Safari; Masumeh Shahsavn; Saeed Kalantari

doi:10.3390/vaccines11020455

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

Vaccines (Basel). 2023 Feb 16;11(2):455. doi: 10.3390/vaccines11020455.

Authors

Masoud Solaymani Dodaran^{1

2

3}, Seyed Reza Banihashemi⁴, Ali Es-Haghi⁵, Mohammad Hossein Fallah Mehrabadi⁶, Mojtaba Nofeli⁷, Ali Rezaei Mokarram⁸, Ladan Mokhberalsafa⁹, Fariba Sadeghi⁹, Alireza Ranjbar¹⁰, Akram Ansarifar¹¹, Arash Mohazzab^{11

12}, Seyed Amin Setarehdan^{3

11}, Fahimeh Bagheri Amiri¹³, Vahideh Mohseni¹¹, Monireh Hajimoradi⁴, Neda Ghahremanzadeh¹¹, Seyed Hossein Razzaz⁴, Safdar Masoomi¹⁴, Maryam Taghdiri⁴, Mohsen Bagheri⁵, Mohsen Lofti⁸, Akbar Khorasani⁷, Masoud Ghader⁵, Shiva Safari¹¹, Masumeh Shahsavn¹¹, Saeed Kalantari¹⁵

Affiliations

¹ Clinical Trial Center, Iran University of Medical Science, Tehran 1449614535, Iran.
² Division of Epidemiology and Public Health, University of Nottingham, Nottingham NG7 2UH, UK.
³ Minimally Invasive Surgery Research Center, Hazrat-e-Rasool Hospital, Iran University of Medical Science, Tehran 1445613113, Iran.
⁴ Department of Immunology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran.
⁵ Department of Physico Chemistry, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran.
⁶ Department of Epidemiology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran.
⁷ Department of Research and Development, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran.
⁸ Department of QA, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran.
⁹ Department of Health, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj P.O. Box 31975/148, Iran.
¹⁰ Institute of Interventional Allergology and Immunology, Bonn/Cologne, 53115 Bonn, Germany.
¹¹ School of Public Health, Iran University of Medical Science, Tehran 1449614535, Iran.
¹² Reproductive Biotechnology Research Center, Avicenna Research Institute Tehran, ACECR, Tehran 1983969412, Iran.
¹³ Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran 1316943551, Iran.
¹⁴ Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran P.O. Box 14115/111, Iran.
¹⁵ Departments of Infectious Diseases and Tropical Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran.

Abstract

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Keywords: SARS-CoV-2; immune response; immunogenicity; intranasal vaccine; recombinant vaccine.

Grants and funding

The sponsor of this study (Razi Vaccine and Serum Research Institute) helped with the design and performed the immunogenicity tests but had no role in data collection, data management, analysis, interpretation, and writing of the report. These were completed by the IUMS clinical trial center. The immunology lab was blinded to the identity of the participants in all blood specimens (see randomization and masking section).