Vaccination against rotavirus is currently the most cost-effective and efficient method for preventing rotavirus infections. In 2009, the World Health Organization (WHO) recommended that all countries include oral rotavirus vaccines in their routine immunization programs¹. Studies have shown that the currently available rotavirus vaccines are generally safe, although their effectiveness evidence varies across different countries and regions. Overall, rotavirus vaccines demonstrate high efficacy and effectiveness in those developed countries in Europe and the Americas, whereas their performance in developing countries in Africa and Asia remains suboptimal ^2-4.

Global Overview of Rotavirus Vaccines

Types of Vaccines

As of now, seven rotavirus vaccines have been approved globally^5,6. These include Rotarix (GlaxoSmithKline, Belgium), RotaTeq (Merck & Co., USA), Rotavac (Bharat Biotech, India), Rotasiil (Serum Institute of India), LLR (Lanzhou Institute of Biological Products, China), LLR3 (Lanzhou Institute of Biological Products, China), and Rotavin-M1 (Polyvac, Vietnam). Among these, RotaTeq, Rotarix, Rotavac, and Rotasiil have received WHO prequalification, while LLR, LLR3, and Rotavin-M1 are licensed for use in select countries (Table 4.1). By 2023, Rotarix was being used in 75 countries and RotaTeq in 24 countries; 11 countries introduced both RotaTeq and Rotarix. Additionally, Rotavac was used in 11 countries, Rotasiil in 6 countries, and a combination of Rotasiil and Rotavac in 1 country. Two countries have announced plans to introduce rotavirus vaccines but have not yet specified products⁷.

Safety, Efficacy, and Effectiveness

Current evidence indicates two widely used rotavirus vaccines’ -Rotarix & RotaTeq- efficacy and effectiveness vary across different countries and regions, which may be attributed to differences in economic levels, lifestyles, genetic backgrounds, and prevalent strains⁵. All approved Rota vaccine products have demonstrated good safety profiles, without reports of severe adverse events following the immunization^12-14,31-33. In general, rotavirus vaccines exhibit higher efficacy and effectiveness in low-mortality regions (primarily the developed countries) compared to high-mortality regions^3,4.

The lower effectiveness of RotaTeq in high-mortality regions may be due to several factors: (1) the predominance of the P[6] genotype in some high-mortality regions, which is not covered by RotaTeq; (2) lower economic levels in high-mortality regions, leading to insufficient vaccine coverage as rotavirus vaccination is not included in national immunization programs; and (3) poorer healthcare and nutritional conditions in high-mortality regions, which prolong the course of rotavirus gastroenteritis (RVGE) and increase the severity and mortality of the disease¹⁵. Other factors, such as malnutrition (zinc and vitamin A/D deficiencies), gut microbiota, multiple infections, immature infant immune systems, environmental enteropathy, maternal antibodies (via placenta or breast milk), and genetic factors, may also contribute to the varying immunogenicity of rotavirus vaccines across countries^16,35. Additionally, the protection of rotavirus vaccine declines more rapidly over time in high-mortality regions¹⁷.

Furthermore, evidence suggests that high vaccination coverage among infants and young children can provide herd protection to older populations. This highlights the potential for broader societal benefits as immunization programs are established. Increasing vaccination coverage and continued investment in comprehensive rotavirus vaccination programs may benefit public health and further reduce the clinical and economic burden of the disease³⁰.

Rotavirus Vaccines Approved in China

Oral Pentavalent Reassortant Rotavirus Vaccine (Vero Cell)

RotaTeq (RV5), an oral pentavalent rotavirus vaccine, was approved in the United States in February 2006 and subsequently used in several European countries. This vaccine consists of five human-bovine (WC3) reassortant strains (G1, G2, G3, G4, and P1A[8]) and is in a three-dose series administered to infants aged 6–32 weeks. The first dose is given at 6–12 weeks of age, with subsequent doses spaced 4–10 weeks apart, and the third dose must be completed by 32 weeks of age. RotaTeq received WHO prequalification in 2008¹⁹ and was launched in China market in 2018.  According to data from Shanghai CDC, the procurement price for this vaccine in Shanghai is 285.5 CNY per dose.

IgA is considered the most acceptable laboratory parameter for assessing the immunogenicity of rotavirus vaccines. It is commonly used as a serological measure in clinical trials. Studies on natural rotavirus infections and vaccine trials have shown a correlation between serum rotavirus antibodies and vaccine protection. A randomized controlled trial in China reported a seroconversion rate of 89.4% for serum IgA following RotaTeq vaccination¹⁸. Another clinical trial evaluated the efficacy and safety of RotaTeq when co-administered with other vaccines, showing that RotaTeq provided 69.3% protection against RVGE of any severity caused by any serotype and 78.9% protection against severe RVGE caused by any serotype¹⁴. China local studies have consistently found that three doses of RotaTeq are highly effective against rotavirus-induced diarrhea. A study in Shanghai reported RotaTeq’s efficacy of 85% (95% CI: 50%–95%) in children aged 14 weeks to 4 years and 97% (95% CI: 83%–100%) in children aged 14 weeks to 2 years, primarily against G8P[8], G9P[8], and G2P[4] strains, which accounted for 78.95%, 18.42%, and 2.63% of prevalent strains, respectively³⁶. In Beijing, the vaccine effectiveness (VE) of three doses of RotaTeq was 90.4% (95% CI: 28.8%–98.7%) against group A rotavirus diarrhea³⁷.

A study conducted in Chengdu found that the introduction of RotaTeq led to a delayed onset of the rotavirus season, a shortened epidemic duration (from 20 to 7 weeks), and a significantly reduced peak positivity rate³⁸. Since its approval in China in 2018, post-marketing surveillance data have shown no severe adverse events associated with large-scale RotaTeq vaccination^19,20. Furthermore, China’s Adverse Events Following Immunization (AEFI) surveillance data for 2020 reported a total of 226,320 AEFI cases, with an overall AFEI reporting rate of 40.94 per 100,000 doses, and 14.37 per 100,000 doses for RotaTeq (RV5 in the Figure) ²⁹.

Oral Rotavirus Live Vaccine

The rotavirus vaccine developed by the Lanzhou Institute of Biological Products in China, known as LLR, is marketed under the brand name “LuoTeWei.” LLR was introduced in China in 2001 but has limited use since rotavirus vaccine has not been included in the national immunization program. The procurement price for LLR in Shanxi Province is 138 CNY per dose in 2024.

Since its introduction in 2001, over 50 million doses of LLR have been administered. Clinical evidence shown that LLR provides certain extent of protection against human rotavirus infections. Previous studies in China have reported lower adverse event rates in LLR recipients compared to control groups, with no cases of intussusception or death, indicating a good safety profile of the vaccine. The incidence of diarrhea was lower in the LLR group than in the control group^21-24. Prospective cohort studies and meta-analyses have shown that LLR provides 69%–72% protection against RVGE and severe RVGE, comparable to the efficacy of rotavirus vaccines produced by GlaxoSmithKline and Merck^21,22. Retrospective studies based on case data and vaccination records have found that one dose of LLR provides protection for children under 5 years of age, particularly against severe RVGE. These studies generally recommend completing the full vaccination schedule as early as possible to maximize protection^39-41. One study in Beijing from 2015 to 2017 reported adjusted vaccine effectiveness (VE) estimates of 36.2% (95% CI: 4.7%–57.3%) and -1.6% (95% CI: -224.5%–68.2%) for children aged 2–35 months and 36–59 months, respectively⁴². A study in Guangzhou from 2002 to 2004 found that the effectiveness of 1 dose LLR was 60.0% in children aged 2–11 months, 80.9% in those aged 12–23 months, and 50% in those aged 24–35 months⁴³.

A study in Shaanxi Province found that Rotavirus vaccination (LLR or RotaTeq) significantly reduced the duration and frequency of vomiting in hospitalized children under 5 years of age⁴⁴. Another study using surveillance data from four cities in Guangdong Province conducted a test-negative case-control study to compare the effectiveness of LLR and RotaTeq against RVGE in hospitalized children from 2020 to 2023. The results showed that both vaccines effectively prevented RVGE, including cases caused by the G8P[8] genotype. Three doses of RotaTeq provided strong protection, while two doses of LLR were also an effective strategy for preventing rotavirus infections²⁵.

Table 4.2 Comparison of LLR and RotaTeq Vaccine Efficacy by Dose and Severity

Vaccine	Doses	Efficacy Against Any RVGE (%)	Efficacy Against Severe RVGE (%)
RotaTeq	1	51.7	67.2
	2	37.6	74
	3	64.1	86.6
LLR	1	38.7	57.7
	2	74.6	73.4
	3	58.8	-27.8

Oral Trivalent Reassortant Rotavirus Vaccine (Vero Cell)

LLR3, a human-lamb reassortant trivalent rotavirus vaccine developed by the Lanzhou Institute of Biological Products, contains G2, G3, and G4 serotypes. A randomized, double-blind, placebo-controlled multicenter study demonstrated that LLR3 has good immunogenicity and protective efficacy against RVGE of any severity RVGE, severe RVGE, and hospitalizations caused by any serotype in Chinese infants¹⁴. LLR3 also showed cross-protection against other RV serotypes, particularly G9, with an efficacy of 70.3% (95% CI: 59.9%–77.9%) against severe RVGE caused by G9. Clinical trials indicated that LLR3 is safe for healthy children aged 2–35 months, with an adverse effect rate of 21.43%. Common adverse reactions included fever, vomiting, and diarrhea, with rates similar to other oral rotavirus vaccines, and no systemic severe adverse reactions were observed . LLR3 was approved for use in China in 2023²³. In 2025, the procurement price of LLR3 is 218 CNY per dose in Xinjiang Autonomous Region.

Rotavirus Vaccines in Development

RV3-BB Vaccine

Among the oral rotavirus vaccines in development, the most ready candidate is RV3-BB, developed by PTBioFarma in Indonesia. This vaccine is based on a naturally attenuated neonatal strain of RV G3P[6] and is currently in clinical trials^3,24. Phase I trials have shown that RV3-BB is well-tolerated in adults, children, and neonates, with good immunogenicity observed in neonates after three doses²⁵.

Oral Hexavalent Recombinant Rotavirus Vaccine (HRV6)
HRV6, developed by the Wuhan Institute of Biological Products, contains six serotypes: G1, G2, G3, G4, G8, and G9, covering 99.6% of the G serotypes of group A rotavirus⁵. Early clinical trials of HRV6 demonstrated good tolerance in both adults and infants, with promising immunogenicity in infants²⁶. A randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial was conducted in Hebei, Hunan, Zhejiang Province, and Guangxi Zhuang Autonomous Region. The results showed no significant differences in the incidence of adverse events and serious adverse events between the HRV6 group and the placebo group²⁷.

Overview of Rotavirus Vaccines in Development in China

Overview of Rotavirus Vaccines in Development in Other Countries

Table 4.4 Overview of Rotavirus Vaccines in Development Internationally

It has been suggested that the next-generation injectable rotavirus vaccines may offer higher protective efficacy, or the combination of oral and injectable vaccines may enhance effectiveness. Furthermore, the study emphasizes that co-administration of the next-generation injectable rotavirus vaccine with the DTP vaccine may effectively improve vaccination coverage and is considered a cost-effective choice. The study supports the necessity of developing injectable rotavirus vaccines⁴⁵.

Content Editor: Siqi Jin, Ziqi Liu

Page Editor：Ziqi Liu

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