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Introduction: Current vaccines vary widely in both their efficacy against infection and disease, and the durability of the efficacy. Some vaccines provide practically lifelong protection with a single dose, while others provide only limited protection following annual boosters. What variables make vaccine-induced immune responses last? Can breakthroughs in these factors and technologies help us produce vaccines with better protection and fewer doses? The durability of vaccine-induced protection is now a hot area in vaccinology research, especially after COVID-19 vaccines lost their luster. It has fueled discussion on the eventual utility of existing vaccines to society and bolstered the anti-vaxxer camp. To sustain public trust in vaccines, lasting vaccines must be developed. Areas covered: This review summarizes licensed vaccines' protection. It analyses immunological principles and vaccine and vaccinee parameters that determine longevity of antibodies. The review concludes with challenges and the way forward to improve vaccine durability. Expert opinion: Despite enormous advances, we still lack essential markers and reliable correlates of lasting protection. Most research has focused on humoral immune responses, but we must also focus on innate, mucosal, and cellular responses – their assessment, correlates, determinants, and novel adjuvants. Suitable vaccine designs and platforms for durable immunity must be found. [ABSTRACT FROM AUTHOR]

Lately, the global incidence of flavivirus infection has been increasing dramatically and presents formidable challenges for public health systems around the world. Most clinically significant flaviviruses are mosquito-borne, such as the four serotypes of dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus and yellow fever virus. Until now, no effective antiflaviviral drugs are available to fight flaviviral infection; thus, a highly immunogenic vaccine would be the most effective weapon to control the diseases. In recent years, flavivirus vaccine research has made major breakthroughs with several vaccine candidates showing encouraging results in preclinical and clinical trials. This review summarizes the current advancement, safety, efficacy, advantages and disadvantages of vaccines against mosquito-borne flaviviruses posing significant threats to human health. [ABSTRACT FROM AUTHOR]

Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases vaccine-mediated immunity may wane rapidly, resulting in either increased susceptibility to that disease or a requirement for more booster vaccinations in order to maintain immunity above a protective level. The durability of antibody responses after infection or vaccination appears to be intrinsically determined by the structural biology of the antigen, with multivalent protein antigens often providing more long-lived immunity than monovalent antigens. This forms the basis for the Imprinted Lifespan model describing the differential survival of long-lived plasma cell populations. There are, however, exceptions to this rule with examples of highly attenuated live virus vaccines that are rapidly cleared and elicit only short-lived immunity despite the expression of multivalent surface epitopes. These exceptions have led to the concept that multivalency alone may not reliably determine the duration of protective humoral immune responses unless a minimum number of long-lived plasma cells are generated by reaching an appropriate antigenic threshold of B cell stimulation. Examples of long-term and in some cases, potentially lifelong antibody responses following immunization against human papilloma virus (HPV), Japanese encephalitis virus (JEV), Hepatitis B virus (HBV), and Hepatitis A virus (HAV) provide several lessons in understanding durable serological memory in human subjects. Moreover, studies involving influenza vaccination provide the unique opportunity to compare the durability of hemagglutinin (HA)-specific antibody titers mounted in response to antigenically repetitive whole virus (i.e., multivalent HA), or detergent-disrupted "split" virus, in comparison to the long-term immune responses induced by natural influenza infection. Here, we discuss the underlying mechanisms that may be associated with the induction of protective immunity by long-lived plasma cells and their importance in future vaccine design. [ABSTRACT FROM AUTHOR]

As a live attenuated vaccine, yellow fever vaccine (YFV) is not routinely performed after allogeneic hematopoietic stem cell transplant (HSCT) despite it being the only efficient preventive therapy. We retrospectively identified 21 HSCT recipients immunized with YFV at a median of 39 months after HSCT and a median of 33 months after withdrawal of immunosuppression without any side effects. Eighteen evaluable patients had protective immunity after YFV. We also observed that a third of the recipients vaccinated with YFV before HSCT had persistent protective immunity after HSCT. [ABSTRACT FROM AUTHOR]

A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity. Methods and Findings: PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07–3.1%). On day 180, these cells were still present (median 0.06%, range 0.02–0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells. Conclusion: The presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35–40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity. [ABSTRACT FROM AUTHOR]

It is estimated that over 2.5 billion people are at risk for contracting dengue, a virus responsible for 50-390 million infections in addition to thousands of hospitalizations and deaths each year.There are no licensed vaccines available to combat this pathogen but substantial efforts are underway to develop live-attenuated, inactivated, and subunit vaccines that will protect against each of the four serotypes of dengue. Unfortunately, the results of a recent Phase IIb efficacy trial involving a tetravalent live-attenuated chimeric dengue virus vaccine have raised questions with regard to our current understanding of vaccine-mediated immunity to this important flavivirus. Here, we will briefly summarize these vaccination efforts and discuss the importance of informative in vivo models for determining vaccine efficacy and the need to establish a quantitative correlate of immunity in order to predict the duration of vaccine-induced antiviral protection. [ABSTRACT FROM AUTHOR]

Yellow fever (YF) vaccination is recommended for persons living in YF-endemic areas as the most effective strategy to reduce the risk for infection (1). The 17D and 17DD live attenuated [...]