The expression analysis of human endogenous retrovirus-K Env, Np9, and Rec transcripts in cervical cancer.

While infection with high-risk human papillomavirus (HPV) types is necessary for cervical cancer (CC) development, it is not enough, and other risk factors are required. Several studies have reported the activation of HERV-K in different cancers; however, the investigation of HERV-K expression levels in CC is scarce. In this study, it was hypothesized that activation of HERV-K could play an essential role in CC development. In this order, the expression levels of HERV-K Env, Np9, and Rec transcripts were investigated on 147 normal to CC uterine cervical tissues using quantitative real-time PCR. The significantly higher levels of HERV-K Env and Np9 transcripts were found in patients with cervical intraepithelial neoplasia (CIN) II-III and CC groups compared to those in the normal/CIN I group. Expression of Rec transcript was also higher only in the CC group than normal/CIN I group. Among CC patients, meaningfully higher levels of HERV-K Env and Np9 transcripts were found in patients with squamous cell carcinoma rather than in adenocarcinoma. When only the HPV 16 positive samples were investigated, it was found that the mean difference in Env and Np9 mRNA levels was meaningfully higher among precancer lesions and the cancer group in comparison with the normal group. However, the Rec mRNA level showed no significant differences. The association between the expression of HERV-K genes was investigated, and a significant positive correlation of Env expression with Np9 transcript was found only in the group with precancer lesions (R = 0.6, p = 0.0037). Moreover, a significant positive correlation was found between Rec and Np9 transcripts in patients with normal cervix tissues (R = 0.26, p = 0.033). However, no correlations were observed between the expression of Env and Rec in the three groups. In conclusion, our results showed that HERV-K transcripts, especially Env and Np9, upregulated during cervical lesion progression. These findings highlight the potential use of HERV-K Env and Np9 as biomarkers for CC diagnosis and prognosis. Further investigation is needed to determine the clinical utility of these markers and whether targeting HERV-K oncogenes could be a viable therapeutic strategy for CC.

Lineage and sublineage analysis of human papillomavirus type 58 in iranian women.

BACKGROUND: Variant analysis of distinct HPV types is important from different aspects including epidemiology, pathogenicity, and evolution. METHODS: For this reason, the full sequence of the E6 and E7 genes of HPV 58 was examined in 130 HPV 58-infected cervical samples using PCR and sequencing. RESULTS: Our results revealed that three lineages A, B, and D were found in this study; among which the B lineage was more common (91.50%). About sublineages, all samples of the B lineage belonged to the B1 sublineage, and samples that were classified as the A and D lineages were found to belong to the A1 (0.77%), A2 (5.38%), A3 (1.50%), and D2 (0.77%) sublineages. No statistically significant differences were found between lineages and stages of disease or amino acid changes (P > 0.05). CONCLUSION: Our results showed that lineage B, sublineage B1, was dominant in Iran. However, more studies with larger sample sizes from different parts of Iran are essential for assessing the pathogenicity risk of HPV 58 lineages in Iranian women with cervical cancer.

The Prevalence of Epstein-Barr Virus in Normal, Premalignant, and Malignant Uterine Cervical Samples in Iran.

INTRODUCTION: It is suggested that Epstein-Barr virus (EBV) may play an important role in cervical cancer development. Most studies found a higher rate of EBV in cervical cancer samples in comparison to premalignant and normal groups. In this regard, this study aimed to investigate the prevalence of EBV in cervical samples. METHODS: In total, 364 samples from 179 healthy subjects, 124 women with premalignant lesions, and 61 patients with cervical cancer were investigated using nested-PCR. RESULTS: The mean age ± SE was 54.1 ± 13.4 in women with cervical cancer, 36.1 ± 9.4 among women with premalignant lesions, and 36.6 ± 11.5 in healthy individuals. In total, 290 out of 364 samples were human papillomavirus (HPV) positive and the following HPV genotypes were detected among them: HPV 16/18 was found in 43.1%, 23.9%, and 65.5% of normal, premalignant, and malignant samples, respectively, and other high-risk types were detected in 56.9% of normal, 76.1% of premalignant, and 34.5% of malignant samples. The prevalence of EBV was found to be 9.8%, 2.4%, and 2.8% in cervical cancer, premalignant lesions, and normal specimens, respectively, and the difference was statistically significant (p = 0.028). The overall frequency of coinfection between EBV and HPV was shown to be 3.6%. The coinfection was more prevalent among HPV 16/18-infected samples than other high-risk HPVs (6.6 vs. 2.9%) although the difference was not reached a statistically significant difference (p = 0.23). CONCLUSION: Our findings indicated that EBV could play an important role as a cofactor in the progression of cervical cancer. However, future studies with larger sample sizes and the expression analysis of EBV transcripts or proteins are mandatory.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Lineage and sublineage analysis of human papillomavirus types 51 and 59 in Iranian women.

The current study aimed to investigate the sequence variations of HPV 51 and 59 in normal cervical cells and premalignant/malignant lesions of the cervix to know the common variants of HPV 51 and HPV 59 circulating in Iran. To do this, eighty-five samples that were infected by HPV 51 or HPV 59 were investigated using hemi-PCR to amplify the E6 gene followed by sequencing. Our findings indicated that lineages A and B were detected in 80.4% and 19.6% of HPV 51-positive cases, respectively. Among samples infected with HPV 59, 32.2% belonged to lineage A and 67.8% were classified with lineage B. In conclusion, our results showed that lineage A of HPV 51 and lineage B of HPV 59 are more prevalent and distributed in Iran.

Molecular characterization of human astrovirus infection in children under 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: co-infection with rotavirus.

Human astroviruses (HAstVs) are considered important causative pathogens of acute gastroenteritis (AGE) in children under 5 years of age worldwide, along with group A rotavirus (RVA), norovirus (NoV), and enteric adenovirus (EAdV). The present study was aimed to both detect HAstV and its co-infections and investigate genetic analysis of circulating HAstV and co-infected virus in hospitalized children under 5 years of age with AGE in Iran. Accordingly, a sum of 200 stool specimens were screened by PCR for HAstV during 2021-2022. The HAstV was found in 0.5% of 200 specimens (n = 1) while was co-infected with RVA. The genetic and phylogenetic analysis indicated HAstV1 genotype, which clustered with viruses from lineage 1b, which has not been previously reported in Iran. The detected RVA strain belonged to G1 lineage II/P[8]-lineage III, which has been reported previously in Iran as the most common strain. The further genetic analysis of RVA VP6 and NSP4 demonstrated an atypical genotype pattern G1P[8]-I1-E2, as a mono-reassortant of a Wa-like genogroup, which appeared to be reassorted with the NSP4 gene of E2 genotype of the G2P[4] DS-1 genogroup. Although the clinical outcomes of the AGE-causing viruses co-infection is not yet entirely clear, it seems that future studies will be helpful to merge clinical and epidemiological data of co-infecting viruses for a more accurate medical and clinical relevance in symptomatic children.

Circulating rotavirus P[8]-lineage IV, unlike P[8]-lineage III, significantly related to nonsecretors status in Iranian children.

Rotavirus (RV) P[8] strains are responsible for the most of the RV infections globally and are significantly associated with the secretor and Lewis positive status. Among the distinct P[8] lineages, different ligand affinities have been detected which can be linked to differences in secretor status associated histo-blood group antigens (HBGAs). Herein, we report the lineages of P[8] strains and their associated secretor and Lewis antigen phenotypes in Iranian children. The phylogenetic tree and sequence analyses showed that the most common detected RV P[8] strain belonged to P[8]-lineage III (92%) and were significantly associated with secretor and Lewis positive status. In contrast, 8% of P[8] strains clustered into the P[8]-lineage IV and were significantly associated with nonsecretor status, implying that lineage IV tends to infect nonsecretor individuals. Furthermore, protein modeling and amino acid analyses of the VP8* glycan binding site of Iranian P[8]-lineage IV strains indicated two residual substitutions (T184V and N216V/I) compared to the P[8]-lineage III strains that might have affected the glycan affinity among P[8]-lineages IV strains. The corresponding residual changes might permit their continued transmission in nonsecretor children in competition with other P[8]-lineages. Although nonsecretors show natural resistant to P[8] strains, but such residual changes might overcome this natural resistance which in turn might indirectly contribute to the decline in the vaccine efficacy in populations where HBGA polymorphism allows their circulation at high frequency.

Molecular characterization of rotavirus infections in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: Emergence of uncommon G9P[4] and G9P[8] rotavirus strains.

The present study was conducted to monitor the genotypes of circulating species A rotavirus (RVA) in Iran and investigate genetic linkages between specific RVA VP7, VP4, VP6, and NSP4 segments. For this purpose, 48 RVA strains were detected during the 2021-2022 seasons. The two combinations of G9P[4] and G9P[8] RVA strains were predominant. However, several other combinations of RVA also were detected. Based on the distribution of I and E genotypes (46 strains) with respect to G and P, the most common strains were G9P[4]-I2-E2 (19.5%), G9P[4]-I2-E1 (6.5%), G9P[4]-I1-E1 (4.3%), G9P[8]-I1-E1 (19.5%), and G9P[8]-I2-E2 (10.9%), which were followed by several other combinations of G and P RVA strains with different pattern of I-E genotypes and also emerging, rare and uncommon strains. The present study described the continued circulation of G9 strains with the emergence of uncommon G9P[4] and G9P[8] reassortants with three and two different I-E genotypes, respectively, which have not been reported previously in Iran. Our findings indicated that these uncommon strains exhibited a unique genotype pattern comprising a mixture of genogroup 1 and 2 genes and suggest the need for further analysis of rare, uncommon, and emerging strains of RVA at all 11 gene segments to determine intergenogroup and intragenotype reassortments.

The interplay between human papillomavirus and vaginal microbiota in cervical cancer development.

Over the past few decades, we have grown accustomed to the idea that human papillomavirus can cause tumors. The genetic and environmental factors that make the difference between elimination of viral infection and the development of cancer are therefore an area of active investigation at present. Microbiota has emerged as an important factor that may affect this balance by increasing or decreasing the ability of viral infection to promote. The female reproductive system has its specific microbiota that helps to maintain health and prevent infection with pathogens. In contrast to other mucosal sites, the vaginal microbiota typically has low diversity and contains few Lactobacillus spp. which by using high-throughput 16s rRNA gene sequencing, classified into five different community state types. According to emerging information, increased diversity of vaginal microbiota and reduced abundance of Lactobacillus spp. contribute to HPV acquisition, persistence, and development of cervical cancer. In this review, the role of normal female reproductive tract microbiota in health, mechanisms which dysbiosis can cause diseases through interaction with microbes and several therapeutic approaches were addressed.

Genetic characterization of P[8] rotavirus strains circulated in Iran between 2009 and 2017.

Group A rotavirus (RVA) is the most common cause of acute gastroenteritis worldwide, which is responsible for causing an estimated 120 000 deaths in children under 5 years of age, which mostly occur in the lower-income countries of Asia and Africa. The G1P[8] is a common genotype of RVA that has spread throughout the world, including Iran and this genotype is present in two commonly used RVA vaccines, RotarixTM and RotaTeqTM . In this study, we investigated the genetic diversity, viral evolution, and differences between antigenic epitopes of Iran's P[8] strains and two licensed vaccines. The phylogenetic and evolutionary analysis was carried out, using MEGA version 6.0 and BEAST, respectively. Antigenic epitopes of VP8* were compared to determine the differences between strains from Iran and RotarixTM and RotaTeqTM . The P[8]-lineages III and IV were found as the predominant P genotype that circulated in Iran. The TMRCA of P[8]-lineages III and IV was estimated in 1987 and 2009, respectively. The P[8]-lineage III strains showed 12 amino acid changes compared to RotarixTM and 10 amino acid changes compared to RotaTeqTM . The P[8]-lineage IV strains showed 10 amino acid variations for both RotarixTM and RotaTeqTM strains. The results revealed that the P[8] strains circulating in Iran differ from RotarixTM and RotaTeqTM strains. To monitor the long-term effects of vaccines on the emergence of P[8] strains with different lineages, routine and successful monitoring of these strains will be crucial.

Co-administration of rotavirus nanospheres VP6 and NSP4 proteins enhanced the anti-NSP4 humoral responses in immunized mice.

Inconveniences associated with the efficacy and safety of the World Health Organization (WHO) approved/prequalified live attenuated rotavirus (RV) vaccines, sounded for finding alternative non-replicating modals and proper RV antigens (Ags). Herein, we report the development of a RV candidate vaccine based on the combination of RV VP6 nanospheres (S) and NSP4112-175 proteins (VP6S + NSP4). Self-assembled VP6S protein was produced in insect cells. Analyses by western blotting and transmission electron microscopy (TEM) indicated expression of VP6 trimer structures with sizes of ≥140 kDa and presence of VP6S. Four group of mice were immunized (2-dose formulation) intra-peritoneally (IP) by either¨VP6S + NSP4¨ or each protein alone (VP6S or NSP4112-175) emulsified in aluminium hydroxide or control. Results indicated that VP6S + NSP4 formulation induced significant anti-VP6 IgG (P < 0.001) and IgA (P < 0.05) as well as anti-NSP4 IgG (P < 0.001) and enhancement of protective immunity. Analyses of anti-VP6S and anti-NSP4 IgG subclass (IgG1 and IgG2a) showed IgG1/IgG2a ≥6 and IgG1/IgG2a ≥3 ratios, respectively indicating Th2 polarization of immune responses. The combination of VP6S + NSP4 proteins emulsified in aluminum hydroxide adjuvant might present a dual universal, efficient and cost-effective candidate vaccine against RV infection.

Rotavirus VP6: involvement in immunogenicity, adjuvant activity, and use as a vector for heterologous peptides, drug delivery, and production of nano-biomaterials.

The first-generation, live attenuated rotavirus (RV) vaccines, such as RotaTeq and Rotarix, were successful in reducing the number of RV-induced acute gastroenteritis (AGE) and child deaths globally. However, the low efficacy of these first-generation oral vaccines, coupled with safety concerns, required development of improved RV vaccines. The highly conserved structural protein VP6 is highly immunogenic, and it can generate self-assembled nano-sized structures, including tubes and spheres (virus-like particles; VLPs). Amongst the RV proteins, only VP6 shows these features. Interestingly, VP6-assembled structures, in addition to being highly immunogenic, have several other useful characteristics that could allow them to be used as adjuvants, immunological carriers, and drug-delivery vehicles as well as acting a scaffold for production of valuable nano-biomaterials. This review provides an overview of the self-assembled nano-sized structures of VP6-tubes/VLPs and their various functions.

Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: State of the art and future prospects.

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which is responsible for a global pandemic that started in late 2019 in Wuhan, China. To prevent the worldwide spread of this highly pathogenic virus, development of an effective and safe vaccine is urgently needed. The SARS-CoV-2 and SARS-CoV share a high degree of genetic and pathologic identity and share safety and immune-enhancement concerns regarding vaccine development. Prior animal studies with first generation (whole virus-based) preparations of SARS-CoV vaccines (inactivated and attenuated vaccine modalities) indicated the possibility of increased infectivity or eosinophilic infiltration by immunization. Therefore, development of second and third generation safer vaccines (by using modern vaccine platforms) is actively sought for this viral infection. The spike (S) protein of SARS-CoVs is the main determinant of cell entry and tropism and is responsible for facilitating zoonosis into humans and sustained person-to-person transmission. Furthermore, 'S' protein contains multiple neutralizing epitopes that play an essential role in the induction of neutralizing antibodies (nAbs) and protective immunity. Moreover, T-cell responses against the SARS-CoV-2 'S' protein have also been characterized that correlate to the IgG and IgA antibody titres in Covid-19 patients. Thus, S protein is an obvious candidate antigen for inclusion into vaccine platforms against SARS-CoV-2 viral infection. This manuscript reviews different characteristics of S protein, its potency and 'state of the art' of the vaccine development strategies and platforms using this antigen, for construction of a safe and effective SARS-CoV-2 vaccine.

A meta-analysis of human papillomavirus prevalence and types among Iranian women with normal cervical cytology, premalignant lesions, and cervical cancer.

In this study, all data from Iran on human papillomavirus (HPV) prevalence and types among women with normal cervical cytology, premalignant lesions, and cervical cancer were obtained and pooled. The overall HPV prevalence was found to be 9% in women with a normal cervix, 55% in atypical squamous cells of undetermined significance or atypia cases, 58% and 69% in women with low and high grade squamous intraepithelial lesions, respectively, and 81% among women with invasive cervical cancer. In all of the studied groups, HPV 16 was the most common HPV type, followed by HPV 18. In conclusion, this meta-analysis revealed that it will be beneficial if current HPV vaccines are integrated into the national vaccination programs of Iran.

Lineage analysis of human papillomavirus types 31 and 45 in cervical samples of Iranian women.

Knowing the regional lineages/sublineages of human papillomavirus 31 (HPV 31) and 45 would be of great importance for further evolutionary, epidemiological, and biological analysis. In this regard, to characterize more common lineages and sublineages of HPV 31 and 45, the sequence variations of E6 gene were investigated in normal, premalignant, and malignant samples collected from the cervix in Iran. In total, 54 HPV 31- and 24 HPV 45-positive samples were analyzed by hemi-nested polymerase chain reaction (PCR) and nested-PCR, respectively. All PCR products were subjected to direct sequencing analysis. The results indicated that all three lineages A, B, and C were detected in HPV 31-positive samples; among which HPV 31 lineage A was dominant as it was found in 66.7% of all samples. HPV 31 lineages B and C were identified in 5.5% and 27.8% of samples, respectively. In HPV 45-infected samples, lineage B comprised of 62.5% of all samples and the remaining 37.5%  belonged to lineage A. In conclusion, our findings showed that lineage A of HPV 31 was predominant in Iran. Lineage B of HPV 45 was also dominant among Iranian women. However, further studies with larger sample size should be addressed to estimate the pathogenicity risk of HPV 31 or HPV 45 lineages/sublineages in the development of cervical cancer among Iranian women.

Lineage and sublineage analysis of human papillomavirus type 56 in cervical samples of Iranian women.

Understanding the regional lineages and sublineages of human papillomavirus type 56 (HPV 56) would be of great importance for further evolutionary, epidemiological, and biological investigations. To identify the distribution of lineages and sublineages of HPV 56 in Iran, the sequence variations of the E6 gene were analyzed in normal, premalignant, and malignant samples obtained from the cervix. In total, 58 HPV 56-positive samples were investigated by nested-PCR and followed by bidirectional direct nucleotide sequencing analysis. Both lineages A and B were identified in the studied samples. Lineage B was dominant as it was detected in 88.4% of all samples and the remaining samples belonged to lineage A (11.6%). Sublineages A1 and A2 were detected in 3.3% and 8.3% of all samples, respectively. With regard to the pathological stages of cervical specimens, no statistically significant differences were found in the three studied groups (p > 0.05). In conclusion, our findings showed that lineage B of HPV 56 was prevalent in Iran. However, further studies with a larger sample size are warranted to estimate the pathogenicity risk of HPV 56 lineages/sublineages to the progression of cervical cancer among Iranian women.

Association between circulating rotavirus genotypes and histo-blood group antigens in the children hospitalized with acute gastroenteritis in Iran.

Rotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo-blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to P[II]. The most common genotype was P[8] (n = 102; 94.4%), while the remaining belonged to P[4] (n = 3; 2.8%) and P[6] (n = 3; 2.8%) genotypes. The P[8] genotype was found to be associated with secretor and Lewis positive status (p < .05).

The prevalence of human herpesvirus 8 in normal, premalignant, and malignant cervical samples of Iranian women.

BACKGROUND: Regard to this fact that the main transmission route of HPV and HHV-8 is via sexual activity, it is reasonable to speculate that coinfection of HPV and HHV-8 may have been played an important role in the development of cervical cancer. The aim of this study was to estimate the prevalence of HHV-8 and the frequency of HPV and HHV-8 coinfection in cervical samples of patients with cervical cancer and healthy individuals. METHODS: In total, 364 samples from 61 patients with cervical cancer, 124 women with premalignant lesions, and 179 healthy individuals were investigated by nested-PCR. RESULTS: The frequency of HHV-8 was found to be 22.9%, 17.7%, and 14.5% in cervical cancer, premalignant lesions, and normal specimens, respectively (P = 0.308). The overall prevalence of coinfection between HHV-8 and HPV was shown to be 16.2%. The HPV prevalence was higher in HHV-8 positive samples than HHV-8 negative specimens in all three studied groups and this difference was reached a statistically significant level (P = 0.002). However, no significant differences were found between HHV-8 positivity and HPV genotypes (P = 0.08). CONCLUSIONS: Our results showed the higher rate of HHV-8 genome detection in cervical cancer group than control group. However, future studies with larger sample sizes and evaluation of expression of HHV-8 proteins are warranted.

Lineage analysis of human papillomavirus type 39 in cervical samples of Iranian women.

BACKGROUND: The data with regards to the regional variants of distinct HPV types is of great value. Accordance with this, this study aimed to investigate the sequence variations of E6 gene and long control region of HPV 39 among normal, premalignant and malignant cervical samples in order to characterize the frequent HPV 39 variants circulating in Tehran, Iran. METHODS: In total, 70 cervical samples (45 normal, 16 premalignant, and 9 malignant samples) infected with HPV 39 were analyzed by nested-PCR and sequencing. RESULTS: Our results revealed that all samples belonged to A lineage. Almost all sequences (98.6%) were classified in A1 sublineage and only one sample (1.4%) was A2 sub lineage. CONCLUSIONS: Our findings showed that lineages A, sublineage A1, is dominant in Tehran, Iran. However, the small sample size was the most important limitations of this study. Further studies with larger sample size from different geographical regions of Iran are necessary to estimate the pathogenicity risk of HPV 39 variants in this population.

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.