Tuchynskaya et al.
Experimental assessment of possible factors associated with tick-borne encephalitis vaccine failure.
Microorganisms. 2021; 9(6):1172. doi: 10.3390/microorganisms9061172
Although TBE vaccines are highly effective, vaccine failures have been reported. Various factors – host and virus-related – can account for such rare breakthrough infections in vaccinated individuals (see also Snapshot week 26/2021). A Russian team has experimentally analyzed this phenomenon in mouse models.
Among the factors that may be responsible at least in animals are host factors like different susceptibility to TBE virus infection in different mouse strains and sex. In non-vaccinated mice, mortality was 100% and 95% of female and male animals when BALB/c mice were infected with the Siberian subtype strain Vasilchenko (VAS, 300 PFU/mouse), while in female ICR mice, 60% mortality was observed, but in male ICR mice susceptibility was not significantly different with 87% mortality. In vaccination and challenge experiments in these mouse strains, a difference was observed between BALB/c and ICR mice regarding disease symptoms and virus specific RNA detection in the brain (neuroinvasion).
In a model, a mild immunosuppression induced with low-dose cyclophosphamide (Cy), the vaccination demonstrated robust protection against disease symptoms, neuroinvasion, and death when Cy was given prior to two doses of vaccine. Clear differences were seen when Cy was applied after vaccination and prior to challenge with either strain Sofjin (Far Eastern subtype) or VAS. The largest number of vaccine failures was observed when Cy was applied before the first and the second vaccine injection.
In addition, investigations were carried out with various ratios between non-infectious and infectious virus particles on the vaccine efficacy, showing that challenge with TBE virus enriched with non-infectious particles led to lower neutralizing antibody titers in vaccinated mice after the challenge but did not affect the protective efficacy.
In summary, the authors present data showing that vaccine failure may be related to a given strain of mice and sex which may affect both susceptibility to the virus and the vaccine efficacy. Also, immuno-suppression of various origins can cause vaccine failure, and here it was shown that in a model Cy has a significant impact at various stages of vaccination and before challenge. Another important factor can be the different strains used for challenge even when the strains belong to the same subtype.
Various factors, or under certain conditions, a combination of various factors, can lead to vaccine failure.