Exploring the potential benefits of mucosal COVID-19 vaccines: opportunities and challenges.

Vaccination remains the primary preventative strategy against COVID-19. Currently, all available vaccines are administered through injection, and there is concern regarding diminishing protection.1Hitchings MDT Ranzani OT Lind ML et al.Change in COVID-19 risk over time following vaccination with CoronaVac: test negative case-control study.BMJ. 2022; 377e070102PubMed Google Scholar, 2Ferdinands JM Rao S Dixon BE et al.Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study.BMJ. 2022; 379e072141PubMed Google Scholar Intranasal, oral, or inhaled vaccines present an alternative immunological approach, stimulating a localised mucosal immune response within the respiratory tract. It is postulated that these mucosal COVID-19 vaccines could offer more sustained and potent protection against SARS-CoV-2 infection.3Mao T Israelow B Peña-Hernández MA et al.Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses.Science. 2022; 378eabo2523Crossref Scopus (31) Google Scholar Furthermore, the induced mucosal immune response might potentially curtail virus transmission from infected individuals.3Mao T Israelow B Peña-Hernández MA et al.Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses.Science. 2022; 378eabo2523Crossref Scopus (31) Google Scholar Administration of mucosal vaccines is uncomplicated, negating the necessity for health-care professionals and needles and streamlining the immunisation process. In The Lancet Infectious Diseases, Li and colleagues4Li J-X Hou LH Gou J-B Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.Lancet Infect Dis. 2023; (published online June 20.)https://doi.org/10.1016/S1473-3099(23)00350-XGoogle Scholar reported the results of an open-label trial to assess the safety and immunogenicity of a heterologous booster regimen using aerosolised Ad5-nCoV. A cohort of 10 059 participants who received the aerosolised Ad5-nCoV booster were included in the safety analysis, with 416 participants included in the immunogenicity analysis. Within 28 days after vaccination, 1299 (13%) patients reported adverse reactions, predominantly mild to moderate in nature. Participants who received aerosolised Ad5-nCoV had significantly elevated levels of neutralising antibodies against the omicron BA.4/5 variant on day 28 compared with those receiving an inactivated vaccine (107·7 [95% CI 88·8–130·7] versus 17·2 [16·3–18·2]). The approved mucosal adenovirus vector vaccines by national agencies in China and India for high-risk groups signifies substantial progress. However, challenges persist, including the necessity to amend these vaccines to counter emerging variants, like omicron.5Afkhami S Kang A Jeyanathan V Xing Z Jeyanathan M Adenoviral-vectored next-generation respiratory mucosal vaccines against COVID-19.Curr Opin Virol. 2023; 01334Crossref PubMed Google Scholar, 6Waltz E China and India approve nasal COVID vaccines—are they a game changer?.Nature. 2022; 609: 450Crossref PubMed Scopus (0) Google Scholar Aerosolised Ad5-nCoV had a modest relative protection of 35·1% (95% CI 23·0–45·2) against COVID-19, compared with the inactivated COVID-19 vaccine, roughly 12 months after the booster during the omicron period.4Li J-X Hou LH Gou J-B Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trial.Lancet Infect Dis. 2023; (published online June 20.)https://doi.org/10.1016/S1473-3099(23)00350-XGoogle Scholar Despite the incremental increase in protection, the use of aerosolised Ad5-nCoV is anticipated to minimally effect transmission amidst the emergence of a new COVID-19 variants. To elucidate the use of mucosal vaccines, additional data are required concerning the immunogenicity of innovative nasal, inhaled, or oral vaccines tailored to the circulating variant, particularly when compared with bivalent mRNA vaccines. Continued investments, exemplified by the allocation of US $5 billion to Operation Next Gen in the USA, reflect a commitment to furthering the research and development of next-generation COVID-19 vaccines, including mucosal formulations.7Reed T White House launching $5B program for next-gen COVID vaccines.https://www.axios.com/2023/04/10/white-house-program-next-gen-covid-vaccinesDate: 2023Date accessed: May 22, 2023Google Scholar Due to their straightforward administration and potential for sterilising immunity, mucosal vaccines could serve as a valuable option for future booster strategies. Nevertheless, more comparative research is needed between different booster regimens over extended periods to evaluate mucosal vaccines' immunogenicity, efficacy, and potential to attenuate transmission. These endeavours could not only address the current pandemic, but also enhance vaccine development for other infectious diseases, including influenza, respiratory syncytial virus, and tuberculosis. I report grants from the National Institutes of Health, Sabin Institute, Butantan Institute, Sanofi, and Merck during the writing of this Comment, and consulting fees from Pfizer, Adium/Moderna, and Takeda outside the submitted work. I am supported by the Oswaldo Cruz Foundation (Edital Covid-19: resposta rápida: 48111668950485). This institutions had no role in the data interpretation, or writing of the Comment. Safety, immunogenicity and protection of heterologous boost with an aerosolised Ad5-nCoV after two-dose inactivated COVID-19 vaccines in adults: a multicentre, open-label phase 3 trialThe heterologous booster regimen with aerosolised Ad5-nCoV is safe and highly immunogenic, boosting both systemic and mucosal immunity against omicron subvariants. Full-Text PDF