key: cord-1009210-mppye8qm
authors: Pawelec, Graham
title: Invited Editorial: Despite COVID-19, Influenza Must Not Be Relegated to “Only the Sniffles”
date: 2020-08-07
journal: Vaccines (Basel)
DOI: 10.3390/vaccines8030445
sha: c551a0eb72b73a2c6fc82bcb7c17272601e0d97f
doc_id: 1009210
cord_uid: mppye8qm

As the current COVID-19 pandemic continues to rage worldwide, it has emerged that the 2019-2020 influenza season has been milder and shorter than usual in the northern hemisphere, presumably due to enforced social distancing [...].

originated from investigations by cancer vaccine developers and which are currently greatly amplified by efforts to produce SARS-CoV-2 vaccines.

Of these new approaches, the use of RNA vaccines is perhaps one of the most likely to yield breakthrough results, as reviewed in the paper by Scorza and Pardi [4] . Much work has been done on developing stabilized forms of RNA for use in vaccines, which can also be self-adjuvanting and do not necessarily need a cold chain for delivery. The latter consideration is not so important in industrialized countries but can be crucial in low-and middle-income countries. Several RNA vaccines have been tested in preclinical models, mostly mouse, but also in those closer to humans, i.e., ferrets and pigs. The pros and cons of self-amplifying influenza virus RNA vaccines, non-replicating influenza virus mRNA vaccines, and industrial development strategies for these vaccines by companies such as Moderna in Boston and CureVac in Tübingen are discussed in this paper. Despite these and other companies currently being "distracted" by COVID-19, clinical trials are ongoing for influenza, which will remain a public health issue beyond the current SAS-CoV-2 pandemic. Thus far, no RNA vaccines have been licensed by the FDA, but it is to be expected that licensing of the influenza vaccines will also receive a boost from the current focus on the "warp speed" development of vaccines against COVID-19.

Regardless of the nature of the vaccine formulation, currently, the efficacy of a vaccine for licensing purposes is established by testing only its ability to induce or increase influenza-specific antibodies. This is the only surrogate of efficiency commonly available. However, it does not guarantee clinical protection, because protection relies on cellular as well as humoral immunity, and even for the latter, it depends on how and which antibodies are assayed. As pointed out by Domnich et al. [5] in a survey of a large number of trials, methods of measuring influenza antibodies vary in different studies, and in less than one-quarter of these is any attempt also made to assess cellular immunity. This makes inter-trial comparisons of the likely efficiency of different and novel vaccines extremely difficult, and this should be a call to arms to standardize and harmonize readouts in published studies. To complicate matters further, Lewnard and Sobey [6] point out that at least some instances of unanticipated failure of even well-matched seasonal influenza vaccines may be due to the different past exposures of different segments of the population to earlier influenza infections. Much of this immune memory will also be mediated by T cells, both as CD4+ helper cells for B cell antibody production and CD8+ cytotoxic cells killing virally-infected host cells, again emphasizing the still-underappreciated importance of cellular immunity.

Much effort is currently being invested in developing vaccines that optimally stimulate such T cell immunity to overcome many of the above problems and provide protection against multiple different influenza strains by targeting antigens shared between them and not varying seasonally, as discussed in the paper by Clemens et al. [7] . This paper has already been the subject of an editorial in this journal [8] and will not be further discussed here.

Taken together, and also considering the many other papers published in the "Influenza Virus Vaccines" section and several other relevant sections of this journal (see https://www.mdpi.com/journal/ vaccines/sections/Influenza_virus_vaccines), it is clear that there remain many scientific, commercial, and public health challenges to overcome before we can really feel comfortable in asserting that we have influenza anywhere near under control. The current focus on COVID-19 must not be allowed to distract us from the continuing seriousness of what is dismissed by many as "only the flu".

Collateral benefits on other respiratory infections during fighting COVID-19

The immune response to influenza in older humans: Beyond immune senescence

Efforts to Improve the Seasonal Influenza Vaccine

New Kids on the Block: RNA-Based Influenza Virus Vaccines

Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials

Immune History and Influenza Vaccine Effectiveness

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

Editorial of Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license

Funding: This research received no external funding.

The authors declare no conflict of interest.