Acceptability for the influenza virus vector COVID-19 vaccine for intranasal spray: A cross-sectional survey in Beijing, China

ABSTRACT

The intranasal spray COVID-19 vaccine was made available for the first time in China, it is necessary to understand receivers’ satisfaction and experience toward the vaccine to help optimize vaccination service. A self-administered multicenter cross-sectional questionnaire survey was conducted in Beijing, China, in December 2022. The vaccination experience was evaluated through three dimensions: immediate tolerance, smooth progress, and time-saving. Vaccine acceptability was measured by receivers’ preference for the intranasal spray over intramuscular injection after vaccination and their recommendation willingness. Stepwise multinomial and binary logistic regression models were applied to investigate factors associated with vaccine acceptability. Among 10,452 participants included in the analysis, 92.6% felt no discomfort during the inoculation, 99.8% thought the vaccination process went well, and 89.4% deemed it a time-saving option. For vaccine acceptability, 5566 (53.3%) participants were willing to recommend the vaccine to others, 534 (5.1%) refused, and 4352 (41.6%) had not decided yet; 6142 (58.8%) participants preferred the intranasal spray, 873 (8.4%) preferred the intramuscular injection, and 3437 (32.9%) had no preferences. The most concerned aspects of the intranasal spray vaccine were vaccine effectiveness and safety. Receivers who perceived higher vaccine effectiveness or safety were more likely to recommend it to others (OR, 95%CI: 4.41, 3.24–6.00; 6.11, 4.52–8.27) or prefer it over intramuscular injection after vaccination (OR, 95%CI: 5.94, 4.62–7.65; 8.50, 6.70–10.78). Receivers showed good acceptability and experience toward the intranasal spray COVID-19 vaccine. Vaccine effectiveness and safety were the most concerned aspects, and corresponding publicity and education efforts may help improve vaccine acceptability.

KEYWORDS:

• Intranasal spray vaccine
• COVID-19
• vaccine acceptability
• recommendation willingness
• vaccine preference

Introduction

The coronavirus disease (COVID-19) pandemic has posed a great burden on human health worldwide. The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the high transmissibility of new variants continuously give rise to new waves of infection.¹ Omicron, the fifth “Variant of Concern (VOC),” was found to have a higher reinfection risk than the Delta variant.² It indicated that the protective effect of existing COVID-19 vaccines or previous SARS-CoV-2 infections may have diminished because of the enhanced immune escape mechanism of the Omicron variant.³ To improve and prolong protective immunity against the disease, several countries have launched second booster COVID-19 vaccination campaigns.^4–6 Sequential booster immunization, a vaccination strategy that uses a booster dose of a heterogeneous type of vaccine, has been recommended for its enhanced protection against COVID-19 infection.^4,7

A vaccine platform is the underlying technology that can be used to develop vaccines. There are five types of COVID-19 vaccine platforms: the whole virus, viral vector, protein subunit, nucleic acid, and virus-like particles vaccines.⁸ In China, multiple roadmaps are adopted to develop COVID-19 vaccines, and 15 vaccines (5 inactivated vaccines, 6 recombinant subunit vaccines, 3 viral vector vaccines, and 1 mRNA vaccine) have been conditionally approved for marketing or emergency use.^9,10 Studies have indicated that mucosal vaccines can mimic the respiratory tract infection of SARS-CoV-2 and activate mucosal and local immunity,¹¹ which may protect against Omicron breakthrough infection.^12,13 Up to date, five COVID-19 mucosal vaccines in India, Russia, and Iran, and two in China have been approved for use,^14,15 including the orally inhaled vaccine developed by CanSino Biologics,¹⁶ Influenza Virus Vector COVID-19 Vaccine for Intranasal Spray co-developed by Hong Kong University, Xiamen University, and Wantai Biopharmaceutical Company¹⁷ in China.

Influenza Virus Vector COVID-19 Vaccine for Intranasal Spray was constructed using the attenuated influenza virus vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, which can also provide cross-protection against H1N1 and H5N1 influenza viruses.¹⁷ Analysis of interim primary data from its phase 3 clinical trial shows that the vaccine offers good protection against Omicron variant strains BA.2, BA.4, and BA.5 (82%) and is well tolerated in adults.¹⁸ The phase III clinical trial also shows that this vaccine is well-tolerated and can be an antibody-independent broad-spectrum effective tool to combat SARS-CoV-2 variants.^19,20 This vaccine is applicable for people 18 years of age and older, including those who have not been immunized against any COVID-19 vaccine, and those who have received one, two, or three previous doses of other COVID-19 vaccines according to the vaccine instruction.

At the beginning of the Omicron wave in China, the second COVID-19 booster campaign was rolled out on December 14, 2022. Population groups with a high risk of infection, people aged 60 and above, people with serious underlying health conditions, and those with low immunity are advised to receive a second booster six months after the first one. Sequential booster immunization was prioritized. For example, those who have received three doses of inactivated vaccines were recommended for a different type of vaccine for the second booster,²¹ namely a recombinant protein vaccine, an adenovirus vector vaccine, or an influenza virus vector vaccine. Influenza Virus Vector COVID-19 Vaccine for Intranasal Spray was one alternative for the second booster.²²

With the rapid evolution of the SARS-CoV-2 and the waning of the protective effect of previous vaccination, mucosal immunity may become a new trend for preventing infection. The intranasal spray COVID-19 vaccine was made available for the first time in Beijing, China,²³ and it is necessary to understand receivers’ satisfaction and experience toward the vaccine to help optimize vaccination service and promote vaccination. Therefore, we conducted a survey in Beijing as the vaccination campaign started, to investigate the acceptability of the intranasal spray COVID-19 vaccine and its associated factors among residents who have received this vaccine.

Materials and methods

Study design and participants

To investigate the receivers’ satisfaction and experience of the intranasal spray COVID-19 vaccine, a cross-sectional survey was jointly designed and conducted by the Beijing Center for Disease Prevention and Control and the School of Population Medicine and Public Health of the Chinese Academy of Medical Science & Peking Union Medical College in Beijing, China. The questionnaire was designed using the online survey platform “wjx” (https://www.wjx.cn). All the vaccination points in four districts (Chaoyang District, Haidian District, Changping District, and Huairou District) were included in this survey, covering urban, suburban, and outer suburban areas in Beijing. The survey started when the implementation plan for the second booster against COVID-19 was released on December 13, 2022. Data collection finished on December 31, 2022. Residents who have finished three doses of the whole-virion inactivated vaccine and came to receive the intranasal spray were invited to participate in the survey. Notably, participants without a recent SARS-CoV-2 infection history were enrolled according to the vaccination guideline that the next vaccine dose is recommended after 6 months of infection during the study period.^24,25 In addition, vaccination staff routinely checked participants’ infection history before giving a vaccination. Participants with a SARS-CoV-2 infection history were those who got infected six months ago. The participants scanned the questionnaire’s quick response (QR) code to participate in this survey during their 30-minute post-vaccination observation period. Informed consent was obtained from each participant online before they completed the questionnaire. The sample size was calculated using the following formula with α = 0.05 and a permissible error of 0.01: $\mathrm{n}=\frac{z_{1-\alpha }^2\ast p\ast \left(1\hspace{0.17em}-\hspace{0.17em}p\right)}{d^2}$. Assuming the acceptability of the intranasal spray COVID-19 will be 50%, a sample size of 9604 was determined. To account for attrition, the sample size was further increased by 10%. Therefore, the final sample size was 10,565.

Those who were aged ≥18 years, agreed to participate in the survey, had finished three doses of the whole-virion inactivated vaccine, and received an intranasal spray booster at one of the survey sites were included in this study. Participants included were all willing to receive the intranasal spray and provided written consent. If someone was unwilling to receive this vaccine, they can choose other types of vaccines later. Those who did not provide written consent, aged younger than 18 years, and whose IP address on the answer sheet was not located in Beijing city were excluded.

Data collection

The questionnaire collected information about sociodemographic characteristics, vaccination experience (immediate tolerance, smooth process, and time-saving), attitudes toward COVID-19 and the intranasal vaccine (perceived vaccine effectiveness and safety, whether prefer the intranasal spray over intramuscular injection after vaccination, and recommendation willingness, etc.), consideration of vaccine administration routes (favorable vaccine characteristics and concerns about the intranasal spray vaccine), social support (whether got family support to get the vaccine), and desired vaccine knowledge from publicity. To make our analysis clearer, the above information was grouped into “Sociodemographic information,” “Thinking and feeling,” “Social process,” “Practical issues,” and “Acceptability” by adapting the WHO’s behavioral and social drivers (BeSD) of vaccination framework.²⁶ In our study, whether receivers prefer the intranasal spray over the intramuscular injection after vaccination and their recommendation willingness were used as proxy indicators of vaccine acceptability or satisfaction.

Statistical analysis

The sociodemographic characteristics, vaccination experience, and vaccine acceptability of participants were analyzed. Continuous and categorical variables were presented as medians (interquartile ranges) and counts (percentages), respectively. The characteristics of participants grouped by vaccine acceptability were described, and chi-squared tests were applied to examine the differences among the groups. Bonferroni correction was applied for multiple comparisons, and the significance level was adjusted. Circle-track figures²⁷ were drawn to describe attitudes and concerns about this vaccine in participants with different vaccine preferences. Venn diagram and the alluvial plot were drawn to show the overlap between the preference and the recommendation willingness regarding the route of vaccination. The health conditions of the participants with different immediate tolerance during vaccination were also described by Circle-track figures (Figure S1). All individuals have no missing data in this survey.

To investigate factors associated with vaccine acceptability, stepwise multinomial and binary logistic regression models were implemented. For preferences of administration routes, preferences of intranasal spray were compared to preferences of intramuscular injection, no preferences, and the combination of the two latter groups separately. For recommendation willingness, being willing to recommend the vaccine to others was compared to refusal, undecided, and the combination of the latter two groups separately. The independent variables included sociodemographic information, attitudes toward COVID-19 and the intranasal vaccine, vaccination experience, consideration of vaccine administration routes, and social support (Table 3). Variables were automatically selected by a stepwise algorithm in logistic regression models. After variable selection, logistic regression models with the selected variables were rebuilt, and the odds ratios (95% confidence intervals) were calculated.

Table 1. Sociodemographic characteristics of participants.

Characteristic	Number of participants (%), N = 10452
Age (Years), Median (Q1-Q3)	41.0 (34.0–49.0)
18–29	1393 (13.3)
30–39	3193 (30.5)
40–49	3388 (32.4)
50–59	2219 (21.2)
≥60	259 (2.5)
Sex
Male	5657 (54.1)
Female	4795 (45.9)
Education level
Middle school or below	2630 (25.2)
High school/Technical Secondary School/Vocational school	2460 (23.5)
Junior college	1754 (16.8)
Bachelor’s degree	2899 (27.7)
Postgraduate or above	709 (6.8)
Occupation
Healthcare workers	2012 (19.2)
Public catering, logistics and delivery workers	2677 (25.6)
Workers for resident services	1222 (11.7)
Staff of party and government organs and social organizations	1916 (18.3)
Others	2625 (25.1)
Underlying diseases
None	8885 (85.0)
Hypertension	844 (8.1)
Sinusitis	270 (2.6)
CVD	131 (1.3)
Chronic diseases of the liver, renal, or tumor	86 (0.8)
Asthma	48 (0.5)
COPD	32 (0.3)
Others	166 (1.6)
SARS-CoV-2 infection history
No	10375 (99.3)
Yes, asymptomatic	42 (0.4)
Yes, mild symptoms	33 (0.3)
Yes, severe symptoms (require hospitalization)	2 (0.0)

Abbreviations: CVD, coronary heart disease or cerebrovascular disease; COPD, chronic obstructive pulmonary disease.

Table 2. Vaccination experience and acceptability of the intranasal spray COVID-19 vaccine.

Vaccination experience and vaccine acceptability	Number of participants (%), N = 10452
Vaccine experience
Immediate tolerance
No discomfort	9673 (92.5)
Slight discomfort	746 (7.1)
Strong discomfort	33 (0.3)
Smooth vaccination process	10426 (99.8)
More time saving than intramuscular injection	9345 (89.4)
Vaccine acceptability
Vaccine preferences
Prefer the intranasal spray	6142 (58.8)
Prefer the intramuscular injection	873 (8.4)
No preferences	3437 (32.9)
Recommendation willingness for this intranasal spray vaccine
Be willing to recommend	5566 (53.3)
Refuse to recommend	534 (5.1)
Not decided yet	4352 (41.6)

Table 3. Factors associated with the preference of vaccine administration routes by stepwise multinomial and binary logistic regression analysis.

	Number of participants (%), N = 10452			p^a	OR (95% CI)
	Preference of intranasal vaccine (n = 6142)	Preference of intramuscular injection (n = 873)	No preferences (n = 3437)		Intranasal spray VS Intramuscular injection^b	Intranasal spray VS No preference^b	Intranasal spray VS intramuscular injection or no preference^c
Sociodemographic information
Education				<.001
High school and below	3158(51.4)	401(45.9)	1531(44.5)		1 [Reference]	1 [Reference]	1 [Reference]
Above high school	2984(48.6)	472(54.1)	1906(55.5)		1.65(1.37–1.99)	1.22(1.07–1.39)	1.29 (1.14–1.46)
Healthcare workers				<.001
No	5111(83.2)	639(73.2)	2690(78.3)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	1031(16.8)	234(26.8)	747(21.7)		0.68(0.55–0.85)	0.82(0.70–0.97)	0.80 (0.69–0.93)
History of asthma				.001
No	6119(99.6)	862(98.7)	3423(99.6)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	23(0.4)	11(1.3)	14(0.4)		0.17(0.07–0.44)	0.55(0.23–1.29)	0.39 (0.18–0.85)
Thinking and feeling
Thinking that intranasal spray is more effective than intramuscular injection				<.001
No or unclear	1583(25.8)	773(88.5)	3024(88.0)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4559(74.2)	100(11.5)	413(12.0)		5.94(4.62–7.65)	4.89(4.23–5.65)	5.08 (4.44–5.81)
Thinking that intranasal spray is safer than intramuscular injection				<.001
No or unclear	1312(21.4)	756(86.6)	3081(89.6)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4830(78.6)	117(13.4)	356(10.4)		8.50(6.70–10.78)	11.29(9.77–13.05)	10.58 (9.26–12.09)
Worrying about the side effect of intranasal spray				<.001
No	1818(29.6)	369(42.3)	986(28.7)		1 [Reference]	1 [Reference]	NA
Yes	4324(70.4)	504(57.7)	2451(71.3)		1.90(1.56–2.30)	0.82(0.71–0.95)	NA
Social process
Thinking that most family members and friends want me to get intranasal spray vaccination				<.001
No or unclear	2015(32.8)	453(51.9)	2269(66.0)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4127(67.2)	420(48.1)	1168(34.0)		1.05(0.88–1.25)	2.06(1.83–2.32)	1.81 (1.61–2.03)
Practical issues
Feeling discomfort during the inoculation process				<.001
No	5819(94.7)	761(87.2)	3093(90.0)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	323(5.3)	112(12.8)	344(10.0)		0.60(0.45–0.80)	0.86(0.69–1.07)	0.80(0.64–0.99)
Thinking that intranasal spray takes less time than intramuscular injection				<.001
No or unclear	365(5.9)	191(21.9)	551(16.0)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	5777(94.1)	682(78.1)	2886(84.0)		2.30(1.82–2.92)	1.54(1.27–1.86)	1.68 (1.40–2.03)
Preferring needle-free				<.001
No	1549(25.2)	478(54.8)	1651(48.0)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4593(74.8)	395(45.2)	1786(52.0)		1.97(1.63–2.39)	1.74(1.52–1.99)	2.11 (1.83–2.43)
Preferring not taking off masks when receiving vaccines				<.001
No	4626(75.3)	420(48.1)	2317(67.4)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	1516(24.7)	453(51.9)	1120(32.6)		0.32(0.27–0.39)	0.68(0.59–0.79)	0.69 (0.59–0.81)
Preferring not taking off clothes when receiving vaccines				<.001
No	1589(25.9)	413(47.3)	1296(37.7)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4553(74.1)	460(52.7)	2141(62.3)		1.69(1.39–2.06)	1.33(1.16–1.53)	1.65 (1.44–1.91)
Preferring no discomfort after inoculation				<.001
No	3493(56.9)	335(38.4)	1431(41.6)		1 [Reference]	1 [Reference]	NA
Yes	2649(43.1)	538(61.6)	2006(58.4)		0.76(0.62–0.94)	0.89(0.77–1.03)	NA
Worrying about respiratory discomfort during inoculation				.126
No	2748(44.7)	398(45.6)	1471(42.8)		1 [Reference]	1 [Reference]	NA
Yes	3394(55.3)	475(54.4)	1966(57.2)		1.43(1.19–1.71)	0.98(0.87–1.12)	NA
Worrying about contraindications (such as asthma, sinusitis, and pulmonary dysfunction)				.674
No	4658(75.8)	671(76.9)	2629(76.5)		1 [Reference]	1 [Reference]	NA
Yes	1484(24.2)	202(23.1)	808(23.5)		1.32(1.07–1.64)	0.97(0.84–1.13)	NA

^aChi-square test was used to compare the difference among different groups of vaccine preferences. Because 15 comparisons were done, Bonferroni correction was applied. The adjusted significance level was approximately 0.003 (0.05/15).

^bOR (95% CI) was estimated from the stepwise multinomial logistic regression.

^cOR (95% CI) was estimated from the stepwise binary logistic regression.

The following candidate variables were included: Sociodemographic information: age groups (<30 years/30–39 years/40–49 years/50–59 years/≥60 years), sex (Male/Female), education level (High school and below/Above high school), healthcare workers (Yes/No), asthma history (Yes/No), sinusitis history (Yes/No), COPD history (Yes/No), CVD history (Yes/No), hypertension history (Yes/No), history of liver or renal diseases, or tumor (Yes/No), other diseases (Yes/No), no diseases (Yes/No), SARS-CoV-2 infection before (No/Yes, asymptomatic/Yes, mild symptoms/Yes, severe symptoms); Thinking and feeling: whether worried about SARS-CoV-2 infection (Do not worried or worried slightly/Worried moderately or strongly), whether think it important to vaccinate against COVID-19 (Yes/No), whether think intranasal spray more effective than intramuscular injection (Yes/No or unclear), whether think intranasal spray safer than intramuscular injection (Yes/No or unclear), whether worried about the effectiveness of intranasal spray (Yes/No), whether worried about the effect of a runny nose or sneeze on vaccine effectiveness (Yes/No), whether worried about the side effect of intranasal spray (Yes/No); Social process: whether think that most family members and friends want me to get intranasal spray vaccination (Yes/No or unclear); Practical issues: whether feel discomfort during vaccination (Yes/No), whether the vaccination process went well (Yes/No), whether think intranasal spray is more timesaving (Yes/No or unclear), whether prefer needle-free (Yes/No), whether prefer not taking off masks (Yes/No), whether prefer not taking off clothes (Yes/No), whether prefer no discomfort after vaccination (Yes/No), whether prefer no bleeding (Yes/No), whether prefer more timesaving administration routes (Yes/No), prefer other vaccine characteristics (Yes/No), whether worried about respiratory discomfort during vaccination (Yes/No), whether worried about service quality (Yes/No), whether worried about contraindications (such as asthma, sinusitis, pulmonary dysfunction) (Yes/No).

SAS (version 9.4; SAS Institute Inc., Cary, NC, USA) and RStudio (version 2022.2.1.461; RStudio Team, 2022) were used to perform data analysis. The stacked-column chart, circle-track figures, Venn diagram, and alluvial plot were drawn with R packages of “ggplot2,” “jjPlot,” “eulerr,” and “ggalluvial” respectively. All statistical tests were two-sided, and a p-value of .05 indicated statistical significance.

Results

Sociodemographic characteristics of the participants

In total, 10648 questionnaires were collected. After excluding those who did not provide the written consent form (n = 80), whose IP address was not located in Beijing city (n = 103), and who were younger than 18 years old (n = 13), 10452 participants were included in the final analysis. The median (interquartile range) age of the participants was 41.0 (34.0–49.0) years, with females accounting for 45.9%. Approximately half of the participants (48.7%) had an education level of high school and below, and 19.2% were healthcare workers. The vast majority of participants (85.0%) reported that they had no underlying diseases; 270 (2.6%) and 48 (0.5%) reported having sinusitis and asthma, respectively. More than 99% of the participants had no history of SARS-CoV-2 infection (Table 1). The sociodemographic characteristics of the participants with different administration route preferences are shown in Table S1.

Vaccination experience and acceptability of the intranasal spray COVID-19 vaccine

In our study, vaccination experience was measured by immediate tolerance, a smooth process, and time-saving. A total of 9673 (92.55%) participants felt no discomfort during vaccination, while 746 (7.14%) and 33 (0.32%) reported slight discomfort and strong discomfort respectively (Table 2). Compared with those who felt no discomfort during inoculation, the proportions of participants with asthma (1.0% VS 0.4%), sinusitis (5.9% vs 2.3%), coronary heart disease or cerebrovascular disease (2.2% VS 1.2%), and hypertension (14.8 VS 7.5%) were larger in those who felt discomfort (Table S3, Figure S1). Nearly all participants (99.75%) said that the vaccination process went well, and the vast majority of participants (89.41%) thought intranasal spray was more time-saving than intramuscular injection (Table 2). The vaccination experience among participants with different vaccine acceptability (whether prefer the intranasal spray over intramuscular injection after vaccination) was also shown. (Table S2).

The vaccine acceptability was indicated by whether receivers preferred the intranasal spray over intramuscular injection after vaccination and their recommendation willingness. For preferences of vaccine administration routes, 6142 (58.8%) participants preferred the intranasal spray, 873 (8.4%) preferred the intramuscular injection, and 3437 (32.9%) had no preference between the two administration routes. For recommendation willingness, 5566 (53.3%) receivers showed a willingness to recommend the intranasal spray vaccine to others, 534 (5.1%) refused, and 4352 (41.6%) had not decided yet (Table 2). To visualize the overlap between the preference and willingness regarding the route of vaccination, the Venn diagram and the alluvial plot were also drawn (Figures S2 and S3).

Concerns about the intranasal COVID-19 vaccine

When participants chose an administration route, the top three factors were “Avoid undressing” (68.4%), “Needle-free” (64.8%), and “No discomfort after vaccination” (49.7%). There is little difference for participants with different vaccine acceptability. For example, those who preferred the intranasal spray prioritized “Needle-free” (74.8%), “Avoid undressing” (74.1%), and “More timesaving” (43.9%) while those who preferred intramuscular injection considered “No discomfort after vaccination” (61.6%), “Avoid undressing” (52.7%), and “Avoid taking off masks” (51.9%) in particular (Figure 1, Table S4).

Figure 1. Considerations of vaccine administration routes (a) Priority factors for vaccination (b) Concerns about the intranasal spray vaccine.

Note: The circle tracks denote preference for intranasal spray vaccine, preference for intramuscular injection, no administration route preference from the outside in. The number in the figure represents the proportion of each item accounting for the total number of answers. It should be multiplied by 3 when calculating what percentage of participants who selected this item because they were allowed to choose three items for the question in the survey.

For this intranasal spray vaccine, participants were most concerned about the effect of a runny nose or sneeze on vaccine effectiveness (69.9%), vaccine side effects (69.6%), and Vaccine effectiveness (68.1%), followed by possible respiratory discomfort after inoculation (55.8%), contraindication (underlying respiratory diseases) (23.9%), service quality (10.3%), and others (2.4%). The concerns of different groups of people with different preferences are also shown (Figure 1a,b, Table S4). In addition, the topics of most interest include vaccine safety (72.7%), vaccine effectiveness (67.6%), how the intranasal spray vaccine works (55.1%), and whether the vaccination is free of cost (51.3%) in the future (Table S5).

Factors associated with vaccine acceptability

Compared with preferences for intramuscular injection or no preferences, the preference for intranasal spray was positively associated with high education level (odds ratio [OR]:1.29, 95% confidence interval [CI]:1.14–1.46) no discomfort during vaccination (OR:1.25, 95% CI:1.01–1.55), high perceived vaccine effectiveness (OR:5.08, 95% CI:4.44–5.81) and safety (OR:10.58, 95% CI:9.26–12.09). Besides, those who favored needle-free (OR:2.11, 95%CI:1.83–2.43), avoiding undressing (OR:1.65, 95% CI:1.44–1.91), no bleeding (OR:1.26, 95% CI:1.09–1.46), and more timesaving (OR:1.19, 95% CI:1.01–1.39), and those who got support from family members or friends (OR:1.81, 95% CI:1.61–2.03) were more likely to have a preference of intranasal spray. However, healthcare workers (OR:0.80, 95% CI:0.69–0.93), those with asthma (OR:0.39, 95% CI:0.18–0.85), and those preferring not taking off their masks when receiving vaccines (OR:0.69, 95% CI:0.59–0.81) showed less vaccine acceptability (Table 3). The willingness to recommend the intranasal spray vaccine to others was also investigated (Table 4). It is noticeable that healthcare workers also showed less acceptability in this dimension (OR: 0.71, 95% CI:0.62–0.80).

Table 4. Factors associated with the recommendation willingness of the intranasal spray vaccine.

	Number of participants (%), N = 10452			p^a	OR (95% CI)
	Willing to recommend (n = 5566)	Refuse to recommend (n = 534)	Not decided (n = 4352)		Willing to recommend VS Refusal ^b	Willing to recommend VS Not decided ^b	Willing to recommend VS Refusal or Not decided ^c
Sociodemographic information
Age group, years				<.001
18–29	601 (10.8)	78 (14.6)	714 (16.4)		1 [Reference]	1 [Reference]	1 [Reference]
30–39	1597 (28.7)	169 (31.6)	1427 (32.8)		1.38(1.01–1.89)	1.34(1.14–1.58)	1.36(1.16–1.60)
40–49	1866 (33.5)	158 (29.6)	1364 (31.3)		1.81(1.31–2.48)	1.73(1.47–2.04)	1.75(1.49–2.06)
50–59	1332 (23.9)	120 (22.5)	767 (17.6)		1.48(1.06–2.07)	1.87(1.57–2.24)	1.86(1.56–2.21)
≥60	170 (3.1)	9 (1.7)	80 (1.8)		2.43(1.13–5.20)	2.15(1.51–3.06)	2.21(1.56–3.12)
Sex				<.001
Female	2209 (39.7)	287 (53.7)	2299 (52.8)		1 [Reference]	1 [Reference]	1 [Reference]
Male	3357 (60.3)	247 (46.3)	2053 (47.2)		1.37(1.11–1.68)	1.31(1.18–1.45)	1.34(1.21–1.48)
Education				<.001
High school and below	3029 (54.4)	263 (49.3)	1798 (41.3)		1 [Reference]	1 [Reference]	NA
Above high school	2537 (45.6)	271 (50.7)	2554 (58.7)		1.51(1.21–1.88)	0.91(0.82–1.02)	NA
Healthcare workers				<.001
No	4748 (85.3)	401 (75.1)	3291 (75.6）		1 [Reference]	1 [Reference]	1 [Reference]
Yes	818 (14.7)	133 (24.9)	1061 (24.4)		0.72(0.56–0.94)	0.73(0.64–0.84)	0.71(0.62–0.80)
Thinking and feeling
Do you think it is important to vaccinate against COVID-19				.002
No	176 (3.2)	27 (5.1)	108 (2.5)		1 [Reference]	1 [Reference]	NA
Yes	5390 (96.8)	507 (94.9)	4244 (97.5)		2.02(1.24–3.30)	0.85(0.62–1.16)	NA
Thinking that intranasal spray is more effective than intramuscular injection				<.001
No or unclear	1465(26.3)	462(86.5)	3453(79.3)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4101(73.7)	72(13.5)	899(20.7)		4.41(3.24–6.00)	3.57(3.16–4.04)	3.65(3.24–4.11)
Thinking that intranasal spray is safer than intramuscular injection				<.001
No or unclear	1342 (24.1)	459 (86.0)	3348 (76.9)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4224 (75.9)	75 (14.0)	1004 (23.1)		6.11(4.52–8.27)	3.79(3.36–4.28)	3.98(3.54–4.48)
Worrying about the effectiveness of intranasal spray				<.001
No	1811 (32.5)	130 (24.3)	1389 (31.9)		1 [Reference]	1 [Reference]	NA
Yes	3755 (67.5)	404 (75.7)	2963 (68.1)		0.73(0.58–0.92)	1.11(0.99–1.24)	NA
Worrying about the side effect of intranasal spray				<.001
No	1537 (27.6)	214 (40.1)	1422 (32.7)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4029 (72.4)	320 (59.9)	2930 (67.3)		1.60(1.29–1.98)	1.17(1.04–1.31)	1.19(1.06–1.33)
Worrying about the effects of a runny nose or sneeze on vaccine effectiveness				.054
No	1687 (30.3)	136 (25.5)	1326 (30.5)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	3879 (69.7)	398 (74.5)	3026 (69.5)		0.65(0.51–0.82)	0.88(0.78–0.99)	0.85(0.76–0.95)
Social process
Thinking that most family members and friends want me to get intranasal spray vaccination				<.001
No or unclear	1709 (30.7)	294 (55.1)	2734 (62.8)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	3857 (69.3)	240 (44.9)	1618 (37.2)		1.34(1.09–1.64)	2.26(2.04–2.51)	2.15(1.95–2.38)
Practical issues
Feeling discomfort during the inoculation process				<.001
No	5281 (94.9)	5281 (94.9)	5281 (94.9)		1 [Reference]	1 [Reference]	NA
Yes	285 (5.1)	285 (5.1)	285 (5.1)		0.51(0.38–0.70)	0.91(0.75–1.11)	NA
Thinking that intranasal spray takes less time than intramuscular injection				<.001
No or unclear	313 (5.6)	130 (24.3)	664 (15.3)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	5253 (94.4)	404 (75.7)	3688 (84.7)		2.61(2.01–3.39)	1.52(1.28–1.81)	1.64(1.38–1.94)
Preferring needle-free				<.001
No	1423 (25.6)	280 (52.4)	1975 (45.4)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4143 (74.4)	254 (47.6)	2377 (54.6)		1.62(1.29–2.03)	1.54(1.37–1.73)	1.63(1.47–1.82)
Preferring not taking off masks when receiving vaccines				<.001
No	4121 (74.0)	254 (47.6)	2988 (68.7)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	1445 (26.0)	280 (52.4)	1364 (31.3)		0.40(0.32–0.50)	0.89(0.79–1.00)	0.85(0.76–0.95)
Preferring not taking off clothes when receiving vaccines				<.001
No	1400 (25.2)	253 (47.4)	1645 (37.8)		1 [Reference]	1 [Reference]	1 [Reference]
Yes	4166 (74.8)	281 (52.6)	2707 (62.2)		1.75(1.40–2.20)	1.37(1.22–1.55)	1.49(1.34–1.66)
Preferring no discomfort after inoculation				<.001
No	3199 (57.5)	211 (39.5)	1849 (42.5)		1 [Reference]	1 [Reference]	NA
Yes	2367 (42.5)	323 (60.5)	2503 (57.5)		0.75(0.59–0.96)	0.89(0.79–1.01)	NA

^aChi-square test was used to compare the difference among different groups of recommendation willingness. Because 17 comparisons were done, Bonferroni correction was applied. The adjusted significance level was approximately 0.003 (0.05/15).

^bOR (95% CI) was estimated from the stepwise multinomial logistic regression.

^cOR (95% CI) was estimated from the stepwise binary logistic regression.

Candidate variables were same as those in Table 3.

Discussion

In China, the recent wave of the COVID-19 epidemic peaked in late December of 2022 and then maintained an almost uniform decline across all provinces. Considering the uncertainty of the epidemic trend and re-infection risk, sequential immunization has become urgent, especially for fragile populations.²⁸ Mucosal boost immunization may become a new trend for its ability to prevent infection by stopping the virus at the site of entry. This study can help us understand receivers’ vaccination experience, satisfaction, and concerns about the intranasal spray COVID-19 vaccine. Additionally, this study is conducted when the intranasal spray vaccination service was first offered in China, and it may also be valuable to other settings that will provide the intranasal spray vaccine service. In our study, about 90% of participants experienced a no-discomfort, time-saving, and smooth vaccination process. More than half of the participants showed a willingness to recommend the vaccine to others or preferred the intranasal spray vaccine over intramuscular injection after this vaccination. The participants’ experience with intranasal spray vaccination was generally good, with 92.6% feeling no discomfort, 99.8% thinking the vaccination process went well, and 89.4% thinking it was timesaving. Among those who experienced discomfort during vaccination, a history of respiratory diseases (such as asthma and sinusitis), cardiovascular diseases or hypertension was more common. It indicated that people with these health conditions were more likely to feel discomfort when vaccinated with the intranasal spray vaccine, but whether they are suitable for this administration route needs to be further investigated. Although people with asthma should use the intranasal vaccine with caution, studies have indicated that this intranasal vaccine was well tolerated and safe even in those with chronic conditions, such as asthma.²⁹

In this study, the vaccine acceptability was well. However, 5%-9% of participants refused to recommend the vaccine or preferred another administration route though they came to receive the intranasal spray. It might be caused by an unpleasant vaccination experience. Recent studies involving preferences of administration routes are mainly conducted in children or parents.^30,31 For example, among children aged 8–12 years, 69% preferred the intranasal vaccine;³⁰ for parents of children with chronic illness, the proportion was 81%.³¹ According to previous studies, the reasons behind the preference for intranasal vaccines were mainly the needle-free or less painful nature of this kind of vaccine,^31,32 while easy administration, habit, and nasal problems were the common reasons behind the preference for intramuscular injection.³¹ In our study, participants who preferred the intranasal spray vaccine valued the needle-free and convenient nature of this vaccine, while those who preferred the intramuscular injection were concerned about the infection risk if taking off masks.

The safety and effectiveness of this new vaccine are the most concerning aspects. About half of the participants showed confidence about the intranasal spray vaccine in terms of effectiveness and safety, which could be explained by that the advantages of the intranasal spray vaccine were widely publicized. For example, it is needle-free and less painful; it can stimulate immune responses in the intranasal and throat mucus membranes, which is highly overlapped with the infection site of the Omicron variant and is promising to block both infection and transmission of COVID-19.²⁹ We found that higher perceived vaccine effectiveness or safety was strongly associated with vaccine acceptability. The odds of preferring the intranasal vaccine over an intramuscular vaccine are nearly six times higher among those who believe the intranasal vaccine to be more effective. Meanwhile, lots of participants were also concerned about the vaccine’s side effects and vaccine effectiveness or worried that the vaccine effectiveness would be influenced by respiratory conditions such as runny nose, sinusitis, and asthma. It is reasonable that participants thought intranasal spray was superior to intramuscular injection in terms of effectiveness and safety but still had some concerns, given that it was newly approved and this type of vaccine was relatively rare. The positive results of the Phase 3 clinical trial for this vaccine may help improve the vaccine confidence of the public, which have been posted as a preprint on Research Square after our study period.²⁰

Factors associated with vaccine acceptability can be categorized into four domains of the behavioral and social drivers of the vaccination framework. For “thinking and feeling,” vaccine confidence was positively associated with vaccine acceptability. As mentioned above, people with high perceived vaccine effectiveness and safety were more likely to show satisfaction with this vaccine. For the “Social process,” social support is another crucial factor for vaccine acceptability.²⁶ As shown in our study, those who received support from family or friends were approximately two times more likely to prefer the intranasal spray vaccine than those who did not. For “practical issues,” better vaccination experience, preference for needle-free or not taking off masks were drivers for vaccine acceptability. For “sociodemographic information,” older age, male sex, and high education level were positively associated with vaccine acceptability, which is consistent with other studies.^33,34 Besides, healthcare workers showed lower vaccine acceptability than non-healthcare workers for both recommendation willingness and preference for intranasal spray. The underlying reasons for their hesitancy need to be investigated further because of their essential role in vaccination promotion.^34,35 In another survey conducted at the same time as this one (not yet published), we found that the primary barrier was fear of infection during the vaccination process. It implies that measures that can reduce SARS-CoV-2 infection risk during vaccination (e.g. outdoor vaccination setting) are warranted especially during a high incidence period.

This study had several limitations. First, it was a convenience sampling survey conducted in only one province in China. However, this multicenter study had a large sample size and covered urban, suburban, and outer suburban areas in Beijing city, which may have increased the representativeness of our study population. Besides, only a small number of participants aged over 60 years were included, and the population representativeness may be insufficient for this group of people. Though no association between age and vaccine acceptability was found, the acceptability of the intranasal spray vaccine could be different for aged people. Second, vaccine side effects were not investigated in this study. Considering that the survey was conducted during the post-vaccination observation period of participants, we only asked them whether they felt discomfort during vaccination. Third, the acceptability for the intranasal spray vaccine may change over time as more information becomes available to the public, but this was not investigated because of the limited study duration.

In conclusion, the intranasal spray COVID-19 vaccine has good acceptability and vaccination experience. However, it should be done with caution in people with respiratory conditions because of possible discomfort during vaccination. Vaccine effectiveness and safety are major concerns about the vaccine, which were found to be strongly associated with vaccine acceptability. Therefore, publicity and education efforts to increase vaccine confidence may help to improve vaccine acceptability. Additionally, the underlying reasons for healthcare workers’ less vaccine acceptability need to be further investigated because of their crucial role in public vaccination behavior.

Author’s contributions

JL, JW, and LF contributed equally as co-last authors. JL, LF, YM, YC, JW conceptualized and designed the study. YM and WL conducted the statistical analysis. YM wrote the first draft of the manuscript. RS, BJ, HW, LY, LS conducted data collection. JL, LF, JW, WY, WL supervised all the writing and editing of the manuscript. All authors read and approved the final manuscript.

Ethical approval statement

The study was approved by the Medical Ethics Committee of the Chinese Academy of Medical Sciences and Peking union Medical College, Beijing, China (CAMS&PUMC-IEC-2022-019). Written informed consent was obtained from all participants.

Acknowledgments

We would like to thank Editage (www.editage.com) for writing support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Supplementary data

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2235963.

Additional information

Funding

This study was supported by Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund Project [grant number: L222028], Beijing Municipal Science & Technology Commission project [grant number: Z221100007922018], and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [grant number: 2021-I2M-1-044]. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.