Malaria Vaccine Polypeptide Engineering for High Antibody Titers
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Solution Overview
Problem
Current malaria vaccines lack efficacy, with none effectively preventing or treating malaria parasite infections, and existing vaccines using the SERA protein have lower antibody titers than those found in individuals with protective immunity.
Innovation Solution
A high-immunogenicity polypeptide, specifically designed from the SERA protein's 8-mer repeat and serine-rich regions, combined with optimal adjuvants like aluminium hydroxide gel, K3 CpG adjuvant, and synthetic hemozoin adjuvant, to enhance immunogenicity and induce high anti-SE36 antibody titers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If recombinant SERA protein is used as a vaccine antigen, then the vaccine can be produced using standard recombinant technology, but the antibody titer obtained is lower than that of Africans who have gained protective immunity
Solution Approach 1:
The SERA protein is divided into functional domains, specifically isolating the N-terminal 47-kDa region containing the 8-mer repeat and serine-rich regions. This segmentation identifies and utilizes the specific immunogenic portions of the protein that elicit protective antibodies, rather than using the entire SERA protein which produces lower antibody titers
Solution Approach 2:
The invention focuses on enhancing the local quality of specific regions within the SERA protein. By engineering polypeptides with amplified 8-mer repeat sequences and optimized serine-rich regions, the vaccine presents enhanced epitopes that mimic the high-titer antibodies found in naturally immune Africans, thereby improving protective efficacy
2Quantity of substance
If high doses of antigen are used to induce protective immunity, then antibody titers can be increased, but the cost and potential side effects increase
Solution Approach 1:
The invention changes the immunogenic parameters of the vaccine antigen by engineering polypeptides with repeated 8-mer sequences and optimized serine-rich regions. This parameter modification enables the antigen to elicit high antibody titers at lower doses, reducing both cost and potential side effects associated with high-dose vaccination
Solution Approach 2:
The vaccine combines multiple elements: the engineered 8-mer repeat polypeptide, specific adjuvants (such as alum or CpG oligonucleotides), and sometimes liposome carriers. This composite formulation enhances immunogenicity at lower doses, achieving protective immunity without the drawbacks of high-dose single-component vaccines
Data Source
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AI summary
The present invention provides a vaccine for preventing and/or treating Plasmodium falciparum infections, which comprises a polypeptide set forth in SEQ ID NO: 1 or represented by formula (1), and an adjuvant. X1-A-B-X2-Y-X3-(Y)n-X4-(Y)n-X5 (1) (In the formula, X1 represents the 1st to 7th amino acid residues in a polypeptide set forth in SEQ ID NO: 1; X2 represents the 73th to 177th amino acid residues; X3 represents the 178th to 258th amino acid residues; X4 represents the 259th to 289th amino acid residues; X5 represents the 290th to 334th amino acid residues; A represents an 8-mer repeat sequence contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; B represents a sequence of a serine-rich region contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; Y represents any one selected from A-A, A-B, and B; and n is an integer of 0 or 1.)