Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2

• Published in: Viruses Vol. 14; no. 6; p. 1262
• Main Authors: Chandrasekar, Shaswath S, Phanse, Yashdeep, Riel, Mariah, Hildebrand, Rachel E, Hanafy, Mostafa, Osorio, Jorge E, Abdelgayed, Sherein S, Talaat, Adel M
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 10.06.2022; MDPI
• Subjects: Analysis; Animal models; Antibodies; Coronaviruses; correlate of protection; COVID-19; COVID-19 vaccines; Deoxyribonucleic acid; Disease transmission; DNA; DNA vaccines; Dosage and administration; Genetic engineering; Glycoproteins; Immune response; Immune response (cell-mediated); Immune response (humoral); Immunization; Immunogenicity; Infections; Intranasal administration; Lungs; Lymphocytes T; Methods; Mucosal immunity; Nanoparticles; nanovaccine; Replication; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Testing; Transgenic animals; Transgenic mice; Vaccines; Vectors (Biology); Viral antibodies; Egypt; United States > US; Grand Island New York
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14061262

Antibody measurements are primarily used to evaluate experimental and approved COVID-19 vaccines, which is unilateral considering our immune responses’ complex nature. Previously, we showed that nanoparticle plasmid DNA adjuvant system, QAC, and MVA based vaccines were immunogenic against SARS-CoV-2. Here, we report on the protective efficacy of systemic humoral and mucosal cell-mediated immune responses in transgenic mice models against SARS-CoV-2 following nanoparticle immunization. Parenteral, intramuscular administration of QAC-based plasmid DNA vaccine-encoding SARS-CoV-2 S and N led to the induction of significant serum neutralizing humoral responses, which reduced viral burden in the lungs and prevented viral dissemination to the brain. In contrast, the mucosal, intranasal administration of a heterologous vaccine elicited significant mucosal cell-mediated immune responses in the lungs that limited lung viral replication. The presented results demonstrate that serum neutralizing humoral and local lung T-cell immune responses are critical for the control of SARS-CoV-2 replication.