Reply letter to “Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018–2019 and 2019–2020 calculated using a retrospective test-negative design”

ABSTRACT

A recent study by Zimmerman et al. (2023) reported non-significant higher relative vaccine effectiveness of recombinant (RIV4) over the standard-dose influenza vaccines (SDIV) against outpatient illness during the 2018–19 and 2019–20 vaccination seasons. We agree with the authors’ conclusions and would like to emphasize minimal difference between RIV4 and SDIV using Number Needed to Vaccinate (NNV). The NNV analysis showed 8.9 for the RIV4 and 10 for the SDIV in the 50–64 age group. In the 65+ age group, the NNV was 10.6 for the RIV4 and 11.4 for the SDIV. This indicates a minimal difference between both vaccines and hence they both can be used in immunization programs to improve vaccine coverage.

KEYWORDS:

• Number needed to vaccinate
• standard-dose quadrivalent vaccine
• recombinant quadrivalent vaccine
• vaccine shortage
• vaccine coverage
• influenza vaccine
• flu

Dear editor

We read with interest the article “Vaccine effectiveness of recombinant and standard-dose influenza vaccines against outpatient illness during 2018–2019 and 2019–2020 calculated using a retrospective test-negative design”¹ demonstrating that though relative vaccine effectiveness (rVE) favored recombinant influenza vaccine (RIV4) over standard-dose influenza vaccines (SDIV), it was not statistically significant. As noted by the authors, this may have been due to the study being underpowered. Nevertheless, we agree with the authors’ conclusions and would like to emphasize the minimal difference between the recombinant and the standard-dose egg-based vaccine using Number Needed to Vaccinate (NNV).

Number Needed to Vaccinate is defined as the number of persons needed to be vaccinated to prevent one outcome. It combines both Vaccine Effectiveness (VE) and the background incidence of disease in the population (NNV = 1/[annual incidence of event in the unvaccinated × VE]). It is a measure that demonstrates the potential benefits/cost-effectiveness of immunization² and helps in public health decisions such as vaccine choice, purchase, and distribution. Equivalently, the NNV can be calculated using NNV = 1/ARR, where ARR is the Absolute Risk Reduction (unvaccinated background rate – vaccinated attack rate).

We calculated the NNV, for the RIV4 and SDIV from a phase 3 pivotal trial of the recombinant quadrivalent vaccine, which was conducted during the 2014–15 season.³ The background rates of 12.4–12.9% for the 2014–15 season were taken from Tokars et al. (2018)⁴ and the attack rates of 1.7–3.6% were taken from Dunkle et al. (2017).³ The analysis showed the following: for 50–64 age group, NNV was 8.9 for the RIV4 and 10 for quadrivalent SDIV; and for the 65+ age group, NNV was 10.6 for the RIV4 and 11.4 for quadrivalent SDIV (Table 1).

Table 1. NNV for the recombinant and standard-dose vaccines.

Age group	Vaccine	Background rate	Attack rate	ARR	NNV	Difference in NNV
50–64	RIV4	12.9%	1.7%	0.129–0.017 = 0.112	1/0.112 = 8.9	1.1
	SDIV4	12.9%	2.9%	0.129–0.029 = 0.100	1/0.100 = 10.0
65+	RIV4	12.4%	3.0%	0.124–0.030 = 0.094	1/0.094 = 10.6	0.8
	SDIV4	12.4%	3.6%	0.124–0.036 = 0.088	1/.088 = 11.4

ARR, Absolute risk reduction; NNV, Number needed to vaccinate; RIV4, recombinant influenza vaccine; SDIV4, quadrivalent standard-dose influenza vaccine.

These results indicate that there is a minimal difference in the NNV between both vaccine types. The study results can be further substantiated by a systematic review evaluating the efficacy, effectiveness and safety of RIV4.⁴ In this review, only two studies met the efficacy inclusion criteria, and only one study³ reported a higher rVE of the RIV4 (in adults aged ≥50 y). It is important to note that this study highlights the significant rVE values only in the 50–64 y age group and not for the 65+ age group. This supports the limited evidence for the efficacy and effectiveness of RIV4 compared with quadrivalent SDIV.

In immunization programs, both vaccines can be used to improve vaccine coverage. In a study evaluating the public health and economic impact of a switch from trivalent to quadrivalent influenza vaccines, vaccine coverage was found to be the most influential parameter on the number of influenza-related cases.⁵ In the current situation of high influenza epidemic⁶ and declining influenza immunity in the population, an increase in vaccine coverage reduces the prevalence or incidence rates of the disease, improves herd immunity, and decreases the need for newer vaccines to protect against new strains. Therefore, getting an influenza vaccine is more important than the type of vaccine chosen. The improved vaccine coverage with any vaccine surpasses the clinical and economic benefits, in comparison to non-vaccination option.⁶

We commend the research team for their dedication and hard work in conducting this study. Their research findings are a valuable contribution with the potential to impact policy and practices in the field of influenza vaccination.

Disclosure statement

Sanjay Hadigal, Laura Colombo, and Scott Haughie are the employees of Viatris. Scott Haughie owns shares in Viatris.

Additional information

Funding

The authors reported that there is no funding associated with the work featured in this article.