The use of non-pharmaceutical interventions (NPIs), such as social distancing, lockdowns and the massive use of masks, have not only largely prevented the spread of SARS-CoV-2, but also of other respiratory viruses such as influenza or respiratory syncytial virus (RSV). This decrease has been so high that, in most countries, the influenza and RSV epidemic has not occurred. Far from being a beneficial fact, this can be problematic, since the absence of circulation of certain pathogens can lead to a decrease in herd immunity against them. This can promote the rise of more serious, longer-lasting epidemics that start sooner. To alleviate the collateral effects that may occur due to the decrease in circulation of viruses such as influenza, it is necessary to increase the production of influenza vaccines, carry out mass vaccination campaigns and focus on vaccinating the main drivers of this virus, children.

Pandemic dynamics and health care responses are markedly different during the COVID-19 pandemic than in earlier outbreaks. Compared with established infectious disease such as influenza, we currently know relatively little about the origin, reservoir, cross-species transmission and evolution of SARS-CoV-2. Health care services, drug availability, laboratory testing, research capacity and global governance are more advanced than during 20th century pandemics, although COVID-19 has highlighted significant gaps. The risk of zoonotic transmission and an associated new pandemic is rising substantially. COVID-19 vaccine development has been done at unprecedented speed, with the usual sequential steps done in parallel. The pandemic has illustrated the feasibility of this approach and the benefits of a globally coordinated response and infrastructure. Some of the COVID-19 vaccines recently developed or currently in development might offer flexibility or sufficiently broad protection to swiftly respond to antigenic drift or emergence of new coronaviruses. Yet many challenges remain, including the large-scale production of sufficient quantity of vaccines, delivery of vaccines to all countries and ensuring vaccination of relevant age groups. This wide vaccine technology approach will be best employed in tandem with active surveillance for emerging variants or new pathogens using antigen mapping, metagenomics and next generation sequencing.

Background: Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines. Methods: Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts’ responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated. Results: The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7–21% and reduce IVE by 4–16%. According to the experts, antigenic drift results in a similar impact on VM (8–24%) and IVE (5–20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons. Conclusions: Expert estimates suggest there is a potential for 9% on average (weighted average of “All strains” over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the <65 age group) if egg adaptations that arise when employing the traditional egg-based manufacturing process are avoided.

Influenza is associated with significant morbidity and mortality worldwide. Whilst vaccination is key for the prevention of influenza infection, there are many factors which may contribute to reduced vaccine effectiveness, including antigenic evolution via both antigenic drift and egg-adaptations. Due to the currently dissociated and indirect evidence supporting both the occurrence of these two phenomena in the egg-based manufacturing process and their effects on vaccine effectiveness, this topic remains a subject of debate. To review the evidence and level of agreement in expert opinion supporting a mechanistic basis for reduced vaccine effectiveness due to egg-based manufacturing, using an expert consensus-based methodology and literature reviews. Ten European influenza specialists were recruited to the expert panel. The overall research question was deconstructed into four component principles, which were examined in series using a novel, online, two-stage assessment of proportional group awareness and consensus. The first stage independently generated a list of supporting references for each component principle via literature searches and expert assessments. In the second stage, a summary of each reference was circulated amongst the experts, who rated their agreement that each reference supported the component principle on a 5-point Likert scale. Finally, the panel were asked if they agreed that, as a whole, the evidence supported a mechanistic basis for reduced vaccine effectiveness due to egg-based manufacturing. All component principles were reported to have a majority of strong or very strong supporting evidence (70-90%). On reviewing the evidence for all component principles, experts unanimously agreed that there is a mechanistic basis for reduced vaccine effectiveness resulting from candidate influenza virus variation due to egg-based manufacturing, particularly in the influenza A/H3N2 strain. Experts pointed to surveillance, candidate vaccine virus selection and manufacturing stages involving eggs as the most likely to impact vaccine effectiveness.

Suboptimal vaccine effectiveness against seasonal influenza is a significant public health concern, partly explained by antigenic differences between vaccine viruses and viruses circulating in the environment. Haemagglutinin mutations within vaccine viruses acquired during serial passage in eggs have been identified as a source of antigenic variation between vaccine and circulating viruses. This study retrospectively compared the antigenic similarity of circulating influenza isolates with egg- and cell-propagated reference viruses to assess any observable trends over a 16-year period. Using annual and interim reports published by the Worldwide Influenza Centre, London, for the 2002–2003 to 2017–2018 influenza seasons, we assessed the proportions of circulating viruses which showed antigenic similarity to reference viruses by season. Egg-propagated reference viruses were well matched against circulating viruses for A/H1N1 and B/Yamagata. However, A/H3N2 and B/Victoria cell-propagated reference viruses appeared to be more antigenically similar to circulating A/H3N2 and B/Victoria viruses than egg-propagated reference viruses. These data support the possibility that A/H3N2 and B/Victoria viruses are relatively more prone to egg-adaptive mutation. Cell-propagated A/H3N2 and B/Victoria reference viruses were more antigenically similar to circulating A/H3N2 and B/Victoria viruses over a 16-year period than were egg-propagated reference viruses.

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(t_RI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan–Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The t_RI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower t_RI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the t_RI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.