In a recent study posted to the bioRxiv* preprint server, researchers determined immunity afforded by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nasal vaccine prospect, sCPD9.
Vaccines are a crucial part of the SARS-CoV-2 pandemic response. As of early 2022, 10 Coronavirus disease 2019 (COVID-19) vaccines meet the standards for safety, effectiveness, and quality of the World Health Organization (WHO)'s emergency use listing (EUL). Currently licensed COVID-19 vaccines are based on the inactivated virus, subunit vaccines, nucleoside-modified messenger ribonucleic acid (mRNA) vaccines, and adenoviral vectors.
However, despite the initial long-term protection against severe disease and high vaccination efficiency of the available COVID-19 vaccines, their ability to protect against infection and symptomatic illness diminishes gradually, especially after the emergence and spread of the SARS-CoV-2 Omicron variant. Furthermore, worldwide vaccination disparities remain disturbingly high. These conditions and the ongoing evolution of SARS-CoV-2 necessitate a more robust COVID-19 vaccine and vaccination approach.
Additionally, COVID-19 vaccinations that are currently licensed are delivered intramuscularly and can effectively produce systemic immunity. On the other hand, these vaccinations are less effective at generating long-lasting mucosal immunoglobulin G (IgG) and IgA responses and tissue-resident memory (Trm) cell responses in the lungs.
About the study
In the current research, the scientists compared preclinical effectiveness and immune reactions to the COVID-19 mRNA BNT162b2 vaccine, the live attenuated virus vaccine prospect sCPD9, and an adenovirus-vectored spike (S) vaccine following single/double vaccination in Syrian hamsters. The team compared distinct strategies of vaccination and assessed possible variations in mucosal and systemic immunity imparted by various vaccines and different prime-boost vaccine schedules that consisted of systemic priming coupled with a respiratory boost.
The vaccinated Syrian hamsters were challenged with the SARS-CoV-2 Delta variant to assess the vaccine-imparted protection. In addition, the study employed single-cell sequencing to determine the adaptive and innate immune responses to virulent SARS-CoV-2 infection and vaccination.
Syrian hamsters were immunized with either one dose, i.e., prime-only test, or two doses, i.e., prime-boost experiment, using the three vaccines investigated. The COVID-19 vaccine candidate sCPD9 was administered intranasally, and the mRNA or adenovirus type 2 (Ad2-S) vaccines were given intramuscularly.
Hamsters were infected with Delta via nasal route three weeks following vaccination in the prime-only test. In the prime-boost study, hamsters were boosted using a second vaccine dose three weeks after the priming shot. Further, two weeks following booster dosing, hamsters were nasally infected with the Delta variant. The hamsters were euthanized on days 2 and 5 following the viral challenge, and blood and sections of the lower and upper airways were taken for viral titrations, quantitative reverse transcription-polymerase chain reaction (RT-qPCR), single-cell sequencing, and histological investigations.
The study results demonstrated that the modified live attenuated SARS-CoV-2 vaccine candidate, sCPD9, conferred higher protection from COVID-19, particularly at the mucosal viral entry points, compared to the two other evaluated vaccines. Importantly, anti-SARS-CoV-2 IgA in the nasal mucosa of hamsters vaccinated with sCPD9 was considerably higher. Heterologous vaccination with an intramuscular mRNA vaccine succeeded by an intranasal sCPD9 boost dose increased COVID-19 immunity.
In contrast to the other cohorts, sCPD9-vaccinated animals had considerably greater protection from tissue damage, lung inflammation, and viral replication. In a prime-only context, the effects of sCPD9 immunization were the greatest across all relevant parameters. Likewise, double sCPD9 vaccination outperformed mRNA-sCPD9 vaccination, double mRNA vaccination, and two-dose adenovirus vaccination in a prime-boost environment. Besides, sCPD9-vaccinated animals had lower stimulated pro-inflammatory gene expression pathways, the primary cause of SARS-CoV-2 infection pathogenesis. In sCPD9-vaccinated hamsters, neuronal cells in the nasal mucosa had lower transcriptional activity.
In addition, the authors discovered many gene expression profiles linked to adaptive immune memory activation in sCPD9-vaccinated animals. They found increased pre-plasmablasts produced from memory B cells and T cell proliferation, indicating fast memory cell activation, in the blood of Delta-challenged hamsters. Furthermore, according to an examination of local pulmonary immune responses, sCPD9-vaccinated hamsters' lungs had considerably more proliferating T cells. A subset of those proliferating T cells had a tissue-resident memory (Trm)-restricted characteristic and was connected to the recognized Trm cluster.
According to the authors, this was the first study illustrating a preclinical inter-platform SARS-CoV-2 vaccine comparison that consisted of a live attenuated vaccine.
The study findings showed that all regimens comprising the live-attenuated COVID-19 vaccine candidate, sCPD9, outperformed the other analyzed SARS-CoV-2 vaccines in terms of effectiveness. The heterologous vaccination regimens encompassing sCPD9 imparted strong immunity against COVID-19. sCPD9 vaccination, combined with COVID-19 mRNA/AD2 vaccines or alone, led to fast differentiation of pre-plasmablasts, diminished tissue damage, robust mucosal and systemic humoral responses, faster recall of memory T cells from lung tissue, and rapid viral clearance.
Collectively, the present study suggested that live-attenuated SARS-CoV-2 vaccinations may have advantages over existing vaccines, particularly when used as a booster, and might offer a strategy for COVID-19 pandemic management.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.