Page 104 - MI-2-1

Microbes & Immunity Advax-adjuvanted typhoid vaccine

Table 2. The pros and cons of potential typhoid vaccine adjuvants
Adjuvant Tradenames Pros Cons
Aluminum salts AdjuPhos , • Low cost • Imparts major Th2 immune bias which may
®
(Alum) Alhydrogel ® • Easy to formulate predispose to allergy/anaphylaxis
• Enhances anti‑Vi response • Does not overcome polysaccharide‑associated
immune suppression
• Only modest enhancement of Vi antibody titers
• Low efficacy in children aged <3 months
Delta inulin‑CpG Advax‑CpG ™ • Low cost • None
oligonucleotide • Easy to formulate
combination • Overcomes polysaccharide‑associated
adjuvant immune suppression
• Strong enhancement of anti‑Vi response
• Induces production of serum bactericidal
antibodies
• Effectively overcomes neonatal immune
hypo-responsiveness in newborns

CpG adjuvant elicited anti‑Vi IgG responses up to 1,000‑ SBA has also been shown to be inversely correlated with
fold higher than those induced by an equivalent dose of the susceptibility to typhoid fever. Anti-Vi antibody and SBA
commercial Typhim Vi vaccine. Notably, the Advax‑CpG levels were not correlated in individuals exposed to natural
24
adjuvanted Typhax vaccine did not induce polysaccharide- infection with S. Typhi in an endemic area. This suggests
52
associated immune suppression with the anti-Vi IgG the main protective S. Typhi antibody responses induced
48
levels increasing after each booster immunization. by natural infection or oral vaccines may be directed
Human data showed Vi antibodies induced by Typhim Vi against S. Typhi LPS, rather than Vi polysaccharide. Vi-DT
immunization decay back to baseline by 24 months post- contains a small amount of endotoxin (9.65 EU/dose)
immunization. By contrast, in immunized macaques the which is within the acceptable range for human vaccines.
49
anti‑Vi IgG responses induced by Advax‑CpG adjuvanted Hence, residual S. Typhi LPS contaminating Vi and Vi-DT
Typhax vaccine were durable and remained well above vaccines may act as an antigen and be responsible for
baseline levels up to 9 months post-immunization. Based inducing antibodies with SBA in vaccinated individuals. 16
24
on the estimated protective level of anti‑Vi IgG of 3.5 EU/ Some studies suggest that anti-Vi IgG contributes to
mL, the antibodies induced by Advax‑CpG adjuvanted reduced disease symptoms and prevention of S. Typhi
15
Typhax seem likely to remain well in excess of this level infection. Bactericidal antibody induced by an oral
8,53
for an extended period that may last many years, thereby attenuated vaccine reduced typhoid severity but did not
avoiding the need for regular boosters every 1 – 2 years. protect against clinical disease in a human challenge
The exceptionally high Vi antibody levels induced by model. The bactericidal activity was attributed to anti-
20
Advax‑CpG adjuvanted Typhax vaccine indicate that LPS antibodies rather than anti-Vi antibodies, and
although the Vi polysaccharide is not conjugated to the the depletion of LPS antibodies significantly reduced
CRM197 carrier protein, the Typhax vaccine is working bactericidal activity. The Advax‑CpG adjuvanted Typhax
20
in a T cell-dependent manner. This was confirmed by vaccine group induced high SBA in addition to high anti-Vi
data showing that the anti-Vi response induced by Advax- IgG. It is possible the SBA was due to anti-LPS antibodies
24
CpG adjuvanted Typhax vaccine was markedly attenuated induced by small amounts of bacterial LPS contaminating
in CD4 T cell‑depleted mice, thereby confirming the the S. Typhi polysaccharide used to make Typhax. Notably,
response to be T cell-dependent. Notably, in NHP, Advax‑ a human phase 1 study of a Vi-conjugate vaccine showed
24
CpG adjuvanted Typhax vaccine achieved peak anti‑Vi only a weak correlation between anti-Vi and SBA titer post-
responses that were approximately 25 times those achieved immunization with a 6-fold increase post-immunization
by Typhim Vi. 24 in SBA in the Vi-conjugate vaccine group and a 4-fold

16
6. Role of serum bactericidal activity (SBA) increase in SBA in the Typhim Vi group. In a previous
study, Advax‑CpG adjuvanted Typhax vaccine drove a
in typhoid vaccines 50-fold increase in SBA post-immunization as compared
SBA has been found to be a strong correlate of protection to the Typhim Vi group which induced only a short-
for bacterial vaccines including those targeted at cholera lived 2-fold increase in SBA. Human typhoid challenge
24
and pneumococcal and meningococcal diseases. 50,51 studies may offer a faster and less expensive way to confirm

Volume 2 Issue 1 (2025) 96 doi: 10.36922/mi.4497