Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses.
Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses.
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DOI：
10.3389/fimmu.2023.1139329
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
接种Vi荚膜多糖（Vi-PS）或蛋白质-Vi伤寒结合疫苗（TCV）可保护成人免受伤寒沙门氏菌感染。TCV在婴儿中提供比Vi-PS更好的保护，并且可能在成人中提供更好的保护。TCV在成人中可能具有上级优势的潜在原因尚未完全了解。在这里，我们用Vi-PS或TCV（Vi缀合至破伤风类毒素或CRM 197）免疫野生型（WT）小鼠和IgG或IgM缺陷的小鼠长达7个月，随后用表达Vi的鼠伤寒沙门氏菌进行或不进行攻击。出乎意料的是，单独的IgM或IgG类似地能够减少组织中的细菌负荷，并且这在对缀合或未缀合的Vi疫苗的响应中观察到，并且与抗体的高亲和力无关。仅在免疫后较长时间（>5个月），观察到用Vi-PS或TCV免疫的小鼠的组织细菌负荷的差异。这些差异与在用TCV加强的小鼠中维持较高水平的抗体应答有关，Vi-PS诱导的IgG滴度下降速率大于TCV。因此，Vi特异性IgM或IgG能够独立地保护免受感染，并且成人中TCV疫苗接种的任何上级保护可能与能够更好地持续的应答有关，而不是与诱导的抗体同种型的差异有关。这些发现表明，提高我们对疫苗应答如何维持的理解，可能有助于如何最大限度地提高结合疫苗对包囊病原体（如沙门氏菌）的保护作用。伤寒
Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood. Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV. Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.
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影响因子：
3.7
作者：
Hart PJ;O'Shaughnessy CM;Siggins MK;Bobat S;Kingsley RA;Goulding DA;Crump JA;Reyburn H;Micoli F;Dougan G;Cunningham AF;MacLennan CA
通讯作者：
MacLennan CA
影响因子：
5.5
作者：
KEITEL, WA;BOND, NL;ROBBINS, JB
通讯作者：
ROBBINS, JB
影响因子：
6.8
作者：
Lebacq, E
通讯作者：
Lebacq, E
影响因子：
3.7
作者：
Arcuri M;Di Benedetto R;Cunningham AF;Saul A;MacLennan CA;Micoli F
通讯作者：
Micoli F
影响因子：
7.4
作者：
Giannelli, Carlo;Raso, Maria Michelina;Micoli, Francesca
通讯作者：
Micoli, Francesca