SARS-CoV-2: Immunity, Challenges with Current Vaccines, and a Novel Perspective on Mucosal Vaccines

Abstract

The global rollout of COVID-19 vaccines has played a critical role in reducing pandemic spread, disease severity, hospitalizations, and deaths. However, the first-generation vaccines failed to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission, partially due to the limited induction of mucosal immunity, leading to the continuous emergence of variants of concern (VOC) and breakthrough infections. To meet the challenges from VOC, limited durability, and lack of mucosal immune response of first-generation vaccines, novel approaches are being investigated. Herein, we have discussed the current knowledge pertaining to natural and vaccine-induced immunity, and the role of the mucosal immune response in controlling SARS-CoV2 infection. We have also presented the current status of the novel approaches aimed at eliciting both mucosal and systemic immunity. Finally, we have presented a novel adjuvant-free approach to elicit effective mucosal immunity against SARS-CoV-2, which lacks the safety concerns associated with live-attenuated vaccine platforms.

Immunogenicity and Tolerability of a SARS-CoV-2 TNX-1800, a Live Recombinant Poxvirus Vaccine Candidate, in Syrian Hamsters and New Zealand White Rabbits

“…Multiple vaccine platform approaches have been used to deliver SARS-CoV-2 spike as a vaccine and elicit neutralizing immune responses, including live attenuated viral vectors (e.g., adenovirus), nucleic acids (primarily mRNA), and protein subunits [ 4 , 5 , 6 , 12 , 13 ]. The combination of quickly waning immunity, especially in the upper respiratory system, and the introduction of new SARS-CoV-2 variants with modified spikes has raised concern about the current vaccines [ 14 , 15 ]. Also, accumulating data suggest the currently approved vaccines are not capable of fully protecting against infection/reinfection due to suboptimal mucosal immunity in the upper respiratory tract [ 16 ].…”

Updated Considerations for the Immunopharmacological Aspects of the “Talented mRNA Vaccines”

“…Overall, the salivary titer and the neutralizing activity were lower than the plasmatic ones. Natural infection was able to induce consistently higher titer than vaccines [ 87 , 88 , 89 , 90 , 91 ], although booster doses increased the titer of salivary IgA as well. Finally, mRNA vaccine administered by intramuscular injection succeeded in eliciting mucosal protection but some alternative vaccinal strategies have been also proposed.…”

Plaque Psoriasis Exacerbation and COVID-19 Vaccination: Assessing the Characteristics of the Flare and the Exposome Parameters

“…Studies also indicate a decline in immunity from COVID-19 vaccines over time, with this reduction being more noticeable in older individuals and those with certain underlying health conditions, such as immunodeficiencies. Considering the fact that a booster dose of the COVID-19 vaccine can elicit a strong antibody response that could protect the individuals from acquiring severe disease, it is evident that booster doses continue to play an important role [ 6 ]. Apart from the beneficial role, host responses to immune responses triggered by COVID-19 vaccination included systemic immune activation at times accelerated to an extent resembling a cytokine storm, with the production of various pro-inflammatory cytokines that participate in the immunopathogenesis of many inflammatory skin disorders, such as psoriasis vulgaris [ 7 ].…”