Researchers evaluate the effectiveness of the live-attenuated vaccine (LAV) sCPD9 in promoting systemic and mucosal immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a recent study published in the journal Nature Microbiology.
Introduction
The present intramuscular delivery of COVID-19 vaccines successfully promotes the generation of neutralizing antibodies, effector and central memory T-cells, germinal center B-cells, long-lived plasma cells, and nasal-resident CD8+ T-cells. In order to stimulate long-lasting mucosal immunoglobulin A (IgA) and immunoglobulin G (IgG) responses as well as pulmonary tissue-resident memory cell responses, intramuscular injections are less effective.
Mucosal antibodies, in particular, play a critical role in lowering viral infectivity and transmission at the point of entry. Due to their local placement, tissue-resident memory cells have quicker recall reactions and can identify cognate antigens early.
Concerning the study
In the current study, researchers contrast the immune responses and preclinical efficacy of the Ad2-spike adenovirus-vectored spike vaccine, LAV sCPD9, and the Pfizer-BioNTech BNT162b2 messenger ribonucleic acid (mRNA) COVID-19 vaccine in Syrian hamsters.
In a heterologous SARS-CoV-2 Delta variant challenge scenario, the effectiveness and mode of action of the tested vaccinations were assessed. To test the efficacy of the vaccine, Syrian hamsters received one dose and were exposed to the SARS-CoV-2 Delta strain 21 days later. Two vaccination doses were given to hamsters, 21 days apart, and 14 days after the booster shot, they contracted the virus.
Challenged hamsters were examined histopathologically to assess any lung damage brought on by infection. To find a link between inflammation levels and cellular responses, single-cell RNA sequencing (scRNA-seq) was done on lung specimens.
By examining the hamsters’ sera obtained before and after vaccination and evaluating their ability to neutralize various SARS-CoV-2 variants at various time points, the humoral responses of the animals were evaluated.
Results
All immunizations prevented the weight loss that the SARS-CoV-2 illness caused in hamsters. Since viral RNA was still present in the respiratory system, the vaccinations did not completely protect against SARS-CoV-2 Delta infection after a single dose. The only vaccine tested that successfully decreased replicating virus titers to undetectable levels within two days of the challenge was the sCPD9 vaccine. (dpc).
Through prime-boost immunization, the SARS-CoV-2 vaccine’s overall effectiveness was increased. Even after the prime-boost immunization, there was still detectable viral RNA in oropharyngeal tissues and lungs in all groups, despite the considerable reduction. However, immunization based on sCPD9 was more successful in lowering viral RNA levels.
Two days after the challenge, replication-competent vial levels in the lungs of the vaccinated animals significantly decreased. (dpc). Regardless of whether the complete immunization series was heterologous or homologous, only the sCPD9 booster vaccine significantly lowered replicating viral proportions below the detection threshold.
After a single vaccine, sCPD9 was also very effective at avoiding inflammation and pneumonia. The decreased levels of consolidated lung regions and the lower levels of bronchitis, edema, and lung inflammation served as evidence for this.
Different immunization schedules in the animals resulted in more pronounced bronchial hyperplasia. Similar results were shown with prime-boost regimens, with the mRNA vaccination showing improved histology outcomes with a homologous boost.
A homologous sCPD9 prime-boost immunization provided superior lung anti-inflammatory protection. The lung transcriptome of hamsters who received sCDP9 vaccinations both heterologously and homologously showed fewer genes associated with infection and inflammation.
When compared to other groups, the sera from people who received the sCPD9 vaccine had a better potential to neutralize the ancestor SARS-CoV-2 variant B.1. The Omicron BA.1 sublineage, Beta and Delta variants, and sCPD9 sera were all successfully neutralized.
In all cohorts, the ability to neutralize Omicron BA.1 was diminished, with sCPD9 sera being associated with considerable neutralization. Due to the challenge of infection, neutralizing antibodies grew over time by five dpc in all groups.
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In comparison to hamsters who only got the primary vaccination, those who received the sCPD9 or mRNA vaccine also developed greater neutralizing antibodies. With Omicron BA.1 having the highest neutralization evasion capability among the studied variations, booster vaccination increased the serum neutralization capacity for different variants.
The SARS-CoV-2 spike, nucleocapsid protein, and open reading frame (ORF)-3a were prominently recognized by IgG antibody responses in hamsters who received the mRNA+sCDP9 and prime-boost sCDP9 vaccines. Comparatively, only IgG reactivity against the spike protein was seen in hamsters immunized with prime-boost mRNA and Ad2.
Conclusions
The study’s conclusions included a comparison of various vaccinations, including a new LAV that offered superior protection against SARS-CoV-2 infection compared to existing COVID-19 vaccine types. These results on improved immunity following heterologous prime-boost vaccination are significant because they concur with other recent research that uses systemic priming and intranasal boosting with Ad-2 vector or mRNA vaccines.
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Animals who received the sCPD9 vaccination had considerably greater anti-SARS-CoV-2 IgA levels in their nasal mucosa. When given the sCPD9 vaccine, animals significantly improved their defenses against virus replication, lung inflammation, and tissue damage. The main characteristics of LAV are probably what caused animals who received sCPD9 to recognize antigens more broadly.
