In this study, we sought to determine if BLV- and BLV+ cows were capable of mounting equivalent immune responses to a boost vaccination with Bovi-Shield. This commercial vaccine was chosen as the stimulus because it is a multivalent vaccine that protects against both viral and bacterial pathogens, and because it is commonly used in commercial dairy operations to vaccinate adult lactating cows. Our results demonstrated that BLV+ cows produced lower antibody titers in response to vaccination and that both B and γδ T lymphocytes from BLV+ cows reacted abnormally to antigen-specific and mitogenic stimulation in vitro. Considering that BLV+ cows exhibited abnormalities in both B and T cell compartments, these data support the hypothesis that BLV-infected dairy cows have impaired immunity after vaccination, although this impairment is not an overall suppression of B and T cell activity.
Cows enrolled in our study demonstrated consistently less secreted IgM and similar IgG1, as well as potentially less IgG2 in BLV+ animals, which is consistent with previous reports of aberrant antibody production in BLV-infected cattle. Previous research demonstrated that IgM+ order Z-YVAD-FMK isolated from BLV+ cows with persistent lymphocytosis (PL) expressed equal Ig-μ (heavy chain) mRNA levels, but expressed lower Ig-λ (light chain) mRNA than both BLV- and BLV+ cows in the alymphocytic (AL) stage of infection (Teutsch and Lewin, 1996). At the protein level, calves experimentally infected with BLV demonstrated a decline in total serum IgM when compared to healthy calves (Meiron et al., 1985), and PL cows produced IgM and IgG1 more slowly and at inconsistent ratios after exposure to a synthetic antigen (Trainin et al., 1976). More recently, it was shown that BLV+ cows produced lower titers of IgG2 in response to the J5 E. coli mastitis vaccine (Erskine et al., 2011a), although IgM and IgG1 titers were unaffected by BLV status; in contrast, another study found that BLV+ cows produced lower IgM and IgG1 titers in response to foot-and-mouth disease virus (FMDV) vaccination, while IgG2 titers were equivalent between BLV- and BLV+ cows (Puentes et al., 2016).
The observed differences in antibody deficiencies reported by these three studies are likely the result of different vaccine antigens and/or adjuvants. Bovi-Shield is multivalent and protective against both viral and bacterial pathogens, while Erskine et al. and Puentes et al. measured antibodies produced only against a single bacterial or viral species, respectively. The observed differences may also be a result of the nuanced differences in immune protection against bacterial versus viral pathogens: Leptospira are spirochetes (Levett, 2001) and E. coli are gram-negative bacteria; BHV1 is an enveloped, double-stranded DNA virus (Muylkens et al., 2007), while FMDV is a non-enveloped single-stranded RNA virus (Gao et al., 2016). In addition, the J5 vaccine was used in dry cows, while our study utilized lactating cows; the FMDV vaccine response was measured over a long period of time, while our study focused on the early vaccine response, and these differences could also affect the results seen in our study. Finally, Puentes et al. cattle received their primary vaccination when BLV infection was already established; our study could not control for when cows were first infected with BLV in relation to how many booster vaccines they received and it is currently unknown how a primary antigenic exposure before or after BLV infection affects the immune system over the lifespan of the animal.
Although our results corroborate previous research and support the hypothesis that BLV+ cows exhibit impaired humoral immunity development in response to vaccination, it is unclear if the observed differences would result in increased susceptibility to the infectious diseases vaccines are meant to protect against. Answering that question requires experimental pathogenic challenge, which was beyond the scope of this project. However, we can make some inferences with the given dataset. While class-switched IgG1 and IgG2 are considered pillars of the memory humoral immune response, memory IgM B cells have been documented in humans and mice and likely have functional importance (Kurosaki et al., 2010), so it is entirely possible that lower IgM in BLV+ cows would negatively affect their ability to combat BHV1 and Leptospira infections.