Introduction
Porcine reproductive and respiratory syndrome virus (PRRSV), an
enveloped, positive-sense, single-stranded RNA virus of the familyArteriviridae and the genus Porarterivirus , is the
aetiological agent of porcine reproductive and respiratory syndrome
(PRRS), which causes enormous economic losses to the global swine
industry (Nathues et al., 2017). PRRSVs can be divided into two distinct
species, Betaarterivirus suid 1 (PRRSV-1) andBetaarterivirus suid 2 (PRRSV-2) (ICTV2021). PRRSV-1 is mainly
prevalent in Europe, and PRRSV-2 is prevalent in America and Asia;
partial subtypes of both PRRSVs can be found across North America,
Europe, and Asia (Shi et al., 2010a; Stadejek et al., 2013). In 2010, a
phylogenetic lineage-based PRRSV typing method was proposed. This
classification system grouped PRRSV-1 strains into four subtypes
(subtype Ⅰ (Global), subtype Ⅰ (Russia), subtype II and Ⅲ) and PRRSV-2
strains into nine lineages (lineage 1-lineage 9) based on phylogenetic
relationships in the ORF5 region (Shi et al., 2010a; Shi et al., 2010b).
Although subtype I (Global) of PRRSV-1 has been reported in Asia and
America, the other subtypes have not been reported in regions other than
Europe (Chen et al., 2011; Dewey et al., 2000; Fang et al., 2007; Lee et
al., 2010; Ropp et al., 2004; Thanawongnuwech et al., 2004). PRRSV-2 has
a high degree of genetic diversity, and the 9 lineages can be further
divided into several sublineages (Shi et al., 2010b). The earliest
reported lineage was lineage 5, which appeared in the United States and
is mainly distributed in the United States, southern Canada and parts of
China (Shi et al., 2010a). Then, lineages 8 and 9 were discovered
throughout the United States (Shi et al., 2010b). However, it is
puzzling that sublineage 8.7 (HP-PRRSV), which was first reported in
China in 2006 with the characteristics of causing high temperatures in
infected pigs and having a high incidence and high mortality, is only
found in Asian countries (Shi et al., 2010b). Lineages 3, 4, 6 and 7
have been identified in only a small number of areas: lineage 3 mainly
in southern China (including the Taiwan region and Hong Kong) (Chueh et
al., 1998; Deng et al., 2015; Shi et al., 2010a; Shi et al., 2010b;
Zhang et al., 2019b), lineage 4 mainly in Japan (Shi et al., 2010b), and
lineages 6 and 7 in the United States(Shi et al., 2010a). Undoubtedly,
lineage 1 has become the most prevalent and diverse lineage within the
American and Asian swine industries(Paploski et al., 2021; Sun et al.,
2020). Through 2021, lineage 1 (NADC30-like and NADC34-like) continued
to be the most prevalent and diverse lineage within the U.S. swine
industry (Makau et al., 2021a; Makau et al., 2021b; Paploski et al.,
2021; Yu et al., 2020). In Peru, 75% of the strains detected were
associated with PRRSV 1‐7‐4 strains (sublineage 1.5; NADC34-like) during
2015‐2017 (Ramirez et al., 2019). In South Korea and Japan, lineage 1
(sublineage 1.8; NADC30-like) comprised the second-largest population of
PRRSVs (Fukunaga et al., 2021; Kim et al., 2021). According to the
latest report, lineage 1 (NADC30-like and NADC34-like) strains accounted
for 64% of positive samples in China, much higher than the proportions
of other lineages (Xu et al., 2022). Unlike PRRSV-1 and other lineage
strains of PRRSV-2, which circulate on only one continent, lineage 1
strains have a global pandemic trend. Furthermore, lineage 1C variants
also threaten the global swine industry (Trevisan et al., 2021).
Due to the large genetic diversity
and complex recombination of NADC30 strains, the pathogenicity of
NADC30-like strains varies greatly (Chen et al., 2018; Li et al., 2021b;
Zhang et al., 2019a). As prototypes of NADC30-like strains, MN184 and
NADC30 have moderate pathogenicity (Brockmeier et al., 2012). The
NADC30-like strains in Korea show mild-to-moderate pathogenicity in
challenged pigs (Jeong et al., 2018; Kwon et al., 2019; Oh et al.,
2019). Additionally, the Japanese strain Jpn5-37 induces moderate
symptoms in animals (Iseki et al., 2016). Some NADC30-like strains in
China show high pathogenicity (JL580, SD17-38, 14LY01-FJ, 14LY02-FJ,
15LY01-FJ, 15LY02-FJ, FJXS15, HBap4-2018, JS18-3) (Chen et al., 2018;
Han et al., 2020; Liu et al., 2017a; Liu et al., 2017b; Zhao et al.,
2015); however, most strains show moderate pathogenicity (HNjz15,
CHsx1401, SD53-1603, SC-d, TJnh1501, SCN17, HB17A, SCya18, HN201605,
FJZ03, FJWQ16, ZJqz21, v2016/ZJ/09-03, FJ1402) (Bian et al., 2017; Sui
et al., 2018; Sun et al., 2016; Wang et al., 2018; Wei et al., 2019;
Zhang et al., 2019a; Zhang et al., 2018; Zhang et al., 2016; Zhou et
al., 2018; Zhou et al., 2019; Zhou et al., 2017). Based on cumulative
data, recombination may be responsible for the pathogenicity variance of
NADC30-like PRRSVs in China, and the pathogenicity tends to be
intermediate between those of the parental strains (Yu et al., 2021).
Prevention and control of PRRSV with vaccines has a long history. As
early as 1994, a PRRSV-2 modified-live virus (MLV) vaccine was first
commercialized in North America (Chae, 2021). In China, there are
currently two types of PRRS vaccines: MLV and killed virus (KV) vaccines
(Li et al., 2022). Nine commercial vaccines are currently used to
control and prevent PRRSV infection in China, including Ingelvac PRRS
MLV/RespPRRS MLV, CH-1R, HuN4-F112, JXA1-P80, R98, TJM-F92, GDr180, PC
and CH-1a (KV) (Li et al., 2021a). Of
these, RespPRRS MLV and R98 are of lineage 5, and the others belong to
lineage 8 (Li et al., 2022). KV vaccines have poor protection against
homologous and heterologous strains (Renukaradhya et al., 2015), and MLV
vaccines can provide adequate protection against genetically homologous
strains (Wang et al., 2021). Unfortunately, existing MLV vaccines offer
only limited protection against NADC30-like strains, which are the main
circulating strains in the country (Bai et al., 2016; Li et al., 2022;
Sun et al., 2018; Wei et al., 2019; Zhang et al., 2016; Zhou et al.,
2017). This limitation may be responsible for the rapid spread of
NADC30-like PRRSVs in China. Therefore, it is necessary to develop a new
vaccine against NADC30-like PRRSVs. In addition, the new vaccine must be
evaluated for its cross-protection effect because of the highly variable
genome sequences among NADC30-like PRRSVs caused by recombination and
rapid mutation. In the present study, we developed an attenuated lineage
1 PRRSV vaccine, SD-R (125th passage of strain SD in
Marc-145 cells), and evaluated its homologous and heterologous
protection effects. SD-R provides safe and effective protection against
homologous NADC30-like PRRSV SD and heterologous NADC30-like PRRSV
HLJWK108-1711 challenge, and therefore can serve as an adequate vaccine
against PRRSV infection in herds. To the best of our knowledge, the
lineage 1 PRRSV vaccine SD-R is the first developed and evaluated
attenuated NADC30-like PRRSV candidate vaccine strain in the world.