key: cord-0900808-xnud2b4d authors: Choudhary, Om Prakash; Priyanka; Mohammed, Teroj A.; Singh, Indraj title: Intranasal COVID-19 vaccines: Is it a boon or bane? date: 2021-09-16 journal: Int J Surg DOI: 10.1016/j.ijsu.2021.106119 sha: 6f03d90607793f1085eefdc8d6daad88f0a5361e doc_id: 900808 cord_uid: xnud2b4d nan 1. Broad immune response: The intranasal vaccines induce both innate and adaptive components of the immune system, including antigen-specific memory T and B cells which are helpful in the induction of a broad immune response-neutralizing IgG, mucosal IgA, and T cell responses [3] . 2. Needle-free administration: Intranasal inoculation is a minimally invasive, simple and needle-free mode of administration. This hasslefree method contributes to further compliance and fewer medical complications (localized infection and/or pain) as opposed to traditional methods that involve needle-based skin puncture. Furthermore, the risk of spreading blood-borne infections is also subdued, as can occur with contaminated injection needles. In addition, injection pain is one of the reasons for vaccine hesitancy among people thus; the non-invasive intranasal vaccines would reduce the vaccine hesitancy and improve the rate of immunization against SARS-CoV-2 globally [4] . 3. Antigen delivery to the site of infection: These vaccines deliver antigen to the site of virus entry and infection (nasal passage), leading to the elicitation of mucosal immunity in the respiratory tract. Mucosal immunity protects the mucosal surfaces of the lungs and upper airways, which are common sites for invasion by the SARS-CoV-2 [3] (Fig. 1 ). 4. More convenient: These vaccines would be easier to store, transport, and administer. Some of these vaccines would even be stable at room temperature, making them easier to ship and potentially improving the vaccine coverage in remote areas, especially at the village level. 5. Easy administration: It is easier to administer the vaccine in the form of a nasal spray, and being non-invasive and needle-free, children and people unable to cope with the sight of a needle may benefit from this. Most of these vaccines do not require double-dose administration like other intramuscularly administered COVID-19 vaccines, such as Covishield (Oxford-AstraZeneca), Covaxin (BBV152), Sputnik V (Gam-COVID-Vac) etc. Further, waiving off the need of trained staff, these can be administered at any small healthcare unit. 6. Additional mode of protection: In the respiratory mucosa, vaccineelicited IgA and resident memory B and T cells provide an effective barrier to infection; and, indeed if the infection does take place, perhaps by a viral variant, the cross-reactive resident memory B and T cells, which encounter antigen earlier and respond more quickly than systemic memory cells, would be able to obstruct viral replication and reduce viral shedding and transmission [5] . 7. High compliance: As per the past experiences, these intranasal vaccines may give good results as compared to the intramuscular vaccines in the children as observed in the live attenuated influenza vaccine (LAIV), which is generally superior to the intramuscular vaccination in the children [4] . Therefore, the intranasal vaccines may ideally suit children as well as adults. 8. Global roll-out: These vaccines would also be able to fulfill the global demand for COVID-19 vaccines, as many of the countries like India, being more populous, face a shortage of COVID-19 vaccines. 1. Sterilizing immunity: Though the intranasal vaccines induce both IgA and IgG antibodies, thereby potentially providing "sterilizing immunity" in the upper respiratory tract (local immunity), it is seen with some candidates that systemic IgG antibodies are not as robust in the lower respiratory tract as at the upper airways. 2. Ineffective long-lasting immunity: Another drawback is their inability to produce effective, long-lasting immunity, thus resulting in a faster waning of immunity. The sticky mucous, which serves as a barrier for pathogens in the respiratory system, may interfere with vaccine access and immune activation resulting in poor immunogenicity and faster diminishing protective immunity 3. Child administration problems: Though this route seems more suitable for the administration of vaccines to young children, however in practice, it has been noticed in the case of the intranasal flu vaccines that kids sneeze right after administration, thus making it far too risky an attempt for something so virulent and lethal. Seasonal allergies in young children also resist smooth administration. 4. Safety-related issues: Another issue is the safety of these vaccines. Since the live attenuated virus (a virus weakened so that it cannot produce disease in an individual) is employed in these vaccines, there is a rare risk of reversion of the attenuation, so the virus can regain its ability to cause disease in the individual. This phenomenon, although extremely rare, has also been observed in the oral polio vaccine. It takes a substantially long time to prove the safety of live attenuated vaccines. An intranasal flu vaccine by a Swiss company, Berna Biotech, was discontinued after being linked with a higher risk of Bell's palsy [6] . In conclusion, the advantages of intranasal COVID-19 vaccines conceivably outweigh its drawbacks. The mucosal and systemic immunity elicited by the intranasal immunization against SARS-CoV-2 can serve as all-round protection against infection as well as transmission. As the global efforts in the form of scientific and frontline involvements are underway to restrict the ongoing COVID-19 pandemic, the intranasal vaccines may serve as a boon by sharing the burden of injectable doubledose vaccines, by serving as an alternative in the present time of limited and inequitable vaccine supplies, as well as a booster to intramuscular vaccines when the supply limitations would be overcome in the coming future. Not commissioned, internally peer-reviewed. This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. This article does not require any human/animal subjects to acquire such approval. Name of the registry: Not applicable. Unique Identifying number or registration ID: Not applicable. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable. All authors report no conflicts of interest relevant to this article. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates, npj Vaccines COVID-19: the crucial role of the nose Airway memory CD4+ T cells mediate protective immunity against emerging respiratory coronaviruses The willingness to receive COVID-19 vaccine and its associated factors: "vaccination refusal could prolong the war of this pandemic"-a systematic review Scent of a vaccine Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland All the authors acknowledge and thank their respective Universities and Institutes. The figure has been created with BioRender (htt ps://biorender.com/). Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijsu.2021.106119.