Full-Lung Prophylaxis against SARS-CoV-2 by One-Shot or Booster Intranasal Lentiviral Vaccination in Syrian Golden Hamsters

• Published in: Vaccines (Basel) 2023-01, Vol.11 (1), p.12
• Main Authors: Vesin, Benjamin, Authié, Pierre, Blanc, Catherine, Fert, Ingrid, Noirat, Amandine, Le Chevalier, Fabien, Wei, Yu, Ku, Min-Wen, Nemirov, Kirill, Anna, François, Hardy, David, Planchais, Cyril, Mouquet, Hugo, Guinet, Françoise, Charneau, Pierre, Majlessi, Laleh, Bourgine, Maryline
• Format: Article
• Language: English
• Subjects: Animal models; Antigens; Coronaviruses; COVID-19; COVID-19 vaccines; cross-neutralization; Cross-protection; Disease control; Disease transmission; Efficiency; Enzymes; Glycoproteins; Hamsters; Infections; Inflammation; Infrared imaging systems; Inoculation; Intranasal administration; intranasal vaccination; lentiviral vectors; Life Sciences; lung inflammation; Lungs; mucosal immunity; Nose; Plasmids; Prophylaxis; Proteins; Respiratory diseases; Respiratory tract; SARS-CoV-2 variants; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Vaccine efficacy; Vaccines; Vectors; Viral diseases; Viruses
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11010012

Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors elicit sterilizing prophylaxis against SARS-CoV-2 in preclinical animal models and are particularly suitable for mucosal vaccination, which is acknowledged as the most effective in reducing viral transmission. Here, we demonstrate that a single intranasal administration of a vaccinal lentiviral vector encoding a stabilized form of the original SARS-CoV-2 Spike glycoprotein induces full-lung protection of respiratory tracts and strongly reduces pulmonary inflammation in the susceptible Syrian golden hamster model against the prototype SARS-CoV-2. In addition, we show that a lentiviral vector encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::S ) prevents pathology and reduces infectious viral loads in lungs and nasal turbinates following inoculation with the SARS-CoV-2 Omicron variant. Importantly, an intranasal boost with LV::S improves cross-seroneutralization much better in LV::S -primed hamsters than in their counterparts primed with an LV-encoding Spike from the ancestral SARS-CoV-2. These results strongly suggest that an immune imprint with the original Spike sequence has a negative impact on cross-protection against new variants. Our results tackle the issue of vaccine effectiveness in people who have already been vaccinated and have vanished immunity and indicate the efficiency of LV-based intranasal vaccination, either as a single dose or as booster.