The public health and the question of the "best vaccine".

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Starting from December 2020, the immunization campaign against SARS-COV-2 has begun in Italy. The Italian Immunization Plan provided for the use of the four vaccines authorized by the European Medicine Agency, two RNA vaccines (Comirnaty, Pfizer and Spikevax, Moderna) and two viral vectored vaccines (Vaxzevria, Astrazeneca and Ad26.COV2.S COVID-19 vaccine, Jansen). [1].

RNA vaccines were recommended for healthcare workers, people aged 80 years or older or affected by chronic conditions that increased the risk of complications in case of COVID; on the other hand, the recommendations about the use of viral vectored vaccines changed more times during the immunization campaign. Viral vectored vaccines were, at the beginning of the immunization campaign, recommended for people younger than 50 years old; in March 2021, these vaccines were suspended for the weeks following the news of some adverse events resulting from the immunization process, specifically thrombosis among young women [2], [3]. Finally, viral vectored vaccines were recommended for people greater than 60 years; in fact, in this age class, the risk of vaccine related thrombosis seemed lower and, so, acceptable. [4].

As in the past, the decision on the viral vectored vaccines suspension was accelerated by judiciary investigation and was not based on the causality assessment of the events reported after vaccine administration. [5].

However, the benefit/risk balance seemed clearly in favor of the vaccination in all age classes. This cessation of the vaccine campaign with Vaxzevria, AstraZeneca vaccine, even if of short duration, has jeopardized trust in vaccines and may have contributed to delaying the deconfinement of the European countries. [3].

In particular, recent studies highlighted that Italy is among the European countries with the highest levels of vaccine hesitancy, mainly because of concerns about vaccine safety and mistrust to public health authorities and other vaccination stakeholders; the experiences of pediatric vaccines showed as the alarming decrease in vaccination rates below the threshold for herd immunity. [6] In Sicily, an Italian Region with around 5 millions of inhabitants, vaccination skepticism caused the rejection of Vaxzevria, Astrazeneca Vaccine and, in May 2021, more than 250.000 doses of this vaccine remained unused and were re-distributed in other Italian regions. This refusal probably caused a delay in the vaccination campaign and an important resurgence of COVID during the summer season, with incidence data higher than in any other Italian Region. [7].

The “Astrazeneca question” re-launched the topic, yet now discussed in the Italian Public Health debate, of the “best vaccine” research. In fact, several HCWs are prone to refuse the use of viral vectored vaccines, because of the pre-licensure data about vaccine efficacy that were different among the marketed products and seemed higher for the RNA vaccines. [8].

This approach lacked of a correct methodology. It must be considered that we cannot compare the results of different trials carried out in different times, among different populations and, also, using different outcomes. The only way to determine if a vaccine is more effective than another is to make a head-to-head comparison in which participants from the same population at the same time are recruited and randomized. The COVID-19 vaccines were tested at different times and under different circumstances. While the RNA vaccines clinical trials targeted the predominate SARS-CoV-2 variant that had arisen in China, viral vectored vaccines trials started after other variants had already emerged. Considering that these variants might result more resistant to the effect of a vaccine, a lower efficacy would be expected. [9], [10].

But the question around the “best vaccines” research does not regard only COVID-19 vaccines. The same debate has, in the past, involved HPV vaccinations [11], the vaccine against pneumococcal disease [12] and, most likely, the discussion on the best products to prevent Herpes Zoster will begin in Italy after the recombinant adjuvanted Herpes Zoster vaccine is available.

The decision about the introduction of a certain vaccine is not based on a mathematical approach, for which Public Health institutions have to choose the vaccine with higher pre-licensure trial efficacy or the vaccine effectiveness from post-marketing data. As recently stated by the Center for Disease Control in the case of pneumococcal vaccines [13], the decision about the vaccination strategies must be based on the evaluation of expected public health impacts and the cost effectiveness connected to the different strategies.[14] The real availability of the different vaccines must also be considered, because, as for COVID19, “the best vaccine is the one you get’’. [9].

In the case of Herpes Zoster vaccines, probably the adjuvanted conjugate vaccine could be the best choice for people affected by primary or secondary immunodepression and the offer of this vaccination for this target group (in particular for young people, actually not included in the National Immunization Schedule [15]) must be accelerated; on the other side, the use of live-attenuated vaccine could be evaluated for the universal mass vaccination of older people, in particular considering the cost of the two vaccines currently available.

Funding.

No fund were requested or obtained to write this article.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.