Vaccine effectiveness against SARS CoV 2: Some scientific data and a breakthrough in sight?
by Prof. Hervé Fleury, MD-PhD | Ventum Biotech Scientific Board Member
SARS-CoV 2 vaccines (we will limit our discussion here to Pfizer/mRNA 1273 Moderna mRNA vaccines BNT162b2 and AstraZeneca recombinant Adenovirus ChAdOx1 nCoV-19 vaccine) have been shown to be effective in reducing the severity of infections and decreasing transfer to intensive care units, especially in patients with risk factors (aged, with diabetes or hypertension, among others) (Voysey et al., lancet 2021; Polack et al. New England Journal of Medicine 2020; Thompson, New England Journal of Medicine 2021). Virologically, efficacy was evaluated by the appearance and increase of neutralizing antibodies directed against "Spike", i.e. the viral protein that binds to the ACE2 cell receptor. It is mainly this parameter that has been used to evaluate primary vaccinations and boosters. It is also this parameter that made it possible to show the partial escape of the "Of concern" variants (the last being BQ.1.1 and XBB.1.5). Antibody kinetics studies have been the basis for boosters to maintain high levels of neutralizing antibodies, particularly against variants, hence the recommendation of 3 injections or even a fourth in at-risk subjects (Barda et al., Lancet 2021; Eliakim Raz et al., JAMA 2021)
It is clear that these vaccines do not have a high preventive efficacy as this one is known for other vaccines (measles, yellow fever for example); The appearance of antibodies is observed but some patients will present an infection associated with viral replication even if they have been vaccinated 3 or 4 times; this notion was reported as early as early 2021 (Bleier et al., Otolaryngol Head Neck Surg 2021). Admittedly, the level of viral synthesis is decreased (although this is disputed) (Singanayagam et al., Lancet Infect Dis. 2022; de Gier et al., Euro Surveill. 2021) and the duration shortened but these subjects will be spreaders of the virus if they do not wear a mask. The vaccines are injectable and generate mainly circulating IgG immunoglobulins that are systemically active but not very effective in the nasopharynx, where IgA immunoglobulins should be generated in the mucous membranes of the tissues of the respiratory tree. This situation is close to that of influenza, as systemic vaccination is not fully protective; this was well known to Russian teams who used live attenuated flu aerosol vaccines; Note that there is currently a quadrivalent live attenuated influenza vaccine that can be used as a nasal spray in the USA and available in Europe (FluMist Quadrivalent). Therefore, while SARS-CoV 2 vaccines have individual efficacy they do not have a pivotal role in controlling infection at the population level (Lipsitch and Dean, Science 2020); it is most likely difficult to achieve viral circulation control without social distancing measures, at least at this time (Bartsch et al., American Journal of Preventive Medicine 2020)
There is an evolution of concerns about the vaccine; Indeed, the search for a more effective vaccine in terms of public health is beginning to integrate projects on vaccination at the mucosal level; some teams are considering trials with nasal instillation followed by injection to generate dual mucosal and systemic protection (Tiboni et al. Int J Pharm 2021).
It was an article published very recently in BioRxiv that prompted me to write this short note; indeed, the Moderna research team (Cambridge, Mass, USA) associated with a team from Galveston (Texas, USA) (Vaca et al., BioRxiv, January 12, 2023) used the SARS CoV 2 mRNA vaccine Moderna nasally to vaccinate hamsters; it can be seen in the figure that two doses of 25ug of intranasal vaccine can generate anti- IgG and IgA anti- spike (which are also neutralizing antibodies) as effectively as intramuscularly; The team then infected the vaccinated hamsters and showed that the viral load in the nasal passages and lungs was lower in the group that received the vaccine intranasally.
All in all, encouraging results that pave the way for a double nasal / intramuscular vaccination that could allow a better control of viral circulation at the population level.
