Travel Vaccines: What’s Needed and Why?

EVERY YEAR, tens of millions of American citizens travel internationally.¹ Many of the places where they visit are developing countries with an omnipresent risk of contracting serious diseases that are rare in the United States, such as cholera, malaria and typhoid fever. The severity of these insidious illnesses can range from mildly to moderately debilitating and can result in coma and even death.

The Centers for Disease Control and Prevention (CDC) warns Americans who travel internationally to take precautions against these illnesses. To assist travelers, CDC publishes the CDC Yellow Book, which provides international travelers and travel health consultants with expert guidance for safe and healthy travel abroad. It includes a list of travel vaccines that Americans might need to get before traveling internationally, depending on their destination, accommodations, activities, duration and travel season. The updated 2024 edition includes a vaccination schedule for travel vaccines, which provides recommended and minimum ages and intervals for travel vaccine doses, country-specific yellow fever vaccine requirements, mosquito avoidance recommendations and malaria prevention guidance.²

Illnesses to Guard Against

When traveling internationally, Americans are most susceptible to mosquito-borne viruses (chikungunya, Japanese encephalitis, malaria, yellow fever and zika virus); bacterial disease spread through contaminated food or water (cholera and typhoid fever); and viral zoonotic disease (rabies). Travelers may contract these viruses through consuming contaminated food or water, getting bitten by a mosquito or sustaining scratches or bites from a rabid animal. This article includes information on transmission, epidemiology and clinical presentation, along with vaccine options approved by the U.S. Food and Drug Administration (FDA) that are available in the United States. CDC recommends that Americans who travel internationally consult with a travel health specialist at least four to six weeks before departure to ensure they receive the most appropriate vaccines for the countries they plan to visit.

Chikungunya

• Clinical description: Chikungunya is a single-stranded RNA virus that belongs to the family Togaviridae, genus Alphavirus. Chikungunya virus is transmitted to humans via the bite of infected Aedes aegypti and Ae. albopictus mosquitos. This virus is found in tropical and subtropical regions, specifically in Africa (there was a recent outbreak on La Reunion, a French island off the coast), the Americas, Asia, Europe and the islands in the Indian and Pacific Oceans. Symptoms include sudden onset of high fever, severe and debilitating joint pain, conjunctivitis, headache, myalgia, nausea, vomiting or rash. Fatalities associated with infection occur but are rare and are most commonly reported in older adults and those with comorbidities.³

• Available vaccines:

– Bavarian Nordic’s Vimkunya single-dose intramuscular vaccine was approved by FDA on Feb. 14, 2025, becoming the first and only virus-like particle (VLP) single-dose chikungunya vaccine for individuals aged 12 years and older. Based on data from two Phase III clinical trials, the vaccine induced neutralizing antibodies in up to 97.8 percent of participants 21 days after vaccination and demonstrated a rapid onset of immune response within one week. “We are proud to provide the first vaccine specifically approved for the prevention of chikungunya virus in individuals aged 12 and over, offering a critical tool to combat this emerging and growing health challenge,” said Paul Chaplin, president and CEO of Bavarian Nordic.⁴

– Valneva’s IXCHIQ vaccine received FDA approval in November 2023 and was launched in March 2024. It is a single 0.5mL dose, live-attenuated vaccine indicated for individuals aged 18 and older. In November 2024, Valneva submitted a label extension application to FDA to extend the use of its IXCHIQ vaccine to adolescents aged 12 to 17 years. Approval of the adolescent indication was expected in May 2025.

Phase III data of Valneva’s IXCHIQ vaccine showed a high and sustained seroresponse rate in adults aged 18 years and older. In December 2024, Valneva reported three-year antibody persistence data showing that 96 percent of participants still enrolled in the trial maintained neutralizing antibody titers well above the seroresponse threshold. The persistence of antibodies in adults aged 65 years and older was comparable to adults aged 18 to 64 years. However, in May of this year, FDA and CDC recommended the IXCHIQ vaccine be paused in individuals 60 years and older due to an ongoing investigation of serious adverse events.5 Studies for age expansion to include younger individuals are underway.

Cholera

• Clinical description: Cholera is an acute bacterial intestinal infection caused by the toxigenic bacterium Vibrio cholerae. The free-living bacterial organism is found in fresh and brackish water and can be transmitted through contaminated food and water. Cholera is endemic to 50 countries, primarily in East and West Africa, South and Southeast Asia and the Caribbean. Symptoms include acute watery diarrhea. However, severe cholera occurs in about 10 percent of individuals, and symptoms include profuse watery diarrhea (often accompanied by nausea and vomiting) that can rapidly lead to severe dehydration and even death if the disease goes untreated.⁶

• Available vaccine: The VAXCHORA vaccine was approved by FDA in 2016 and is the only FDA-licensed vaccine to prevent cholera. This single-dose oral vaccine is indicated for use in children at least 2 years old and adults up to 64 years old. Clinical studies showed that VAXCHORA reduced the risk of moderate to severe diarrhea by 90 percent at 10 days and 80 percent at three months post-vaccination.

Japanese Encephalitis

• Clinical description: Japanese encephalitis (JE) is a single-stranded RNA virus that belongs to the genus Flavivirus. JE virus is transmitted to humans through the bite of an infected Culex mosquito. JE occurs throughout most of Asia and parts of the western Pacific. Most people infected with JE virus are asymptomatic. However, a small percentage of infected people develop encephalitis (inflammation of the brain) with symptoms including fever, headache, vomiting, disorientation, seizures, weakness and coma. Among people who develop encephalitis, the fatality rate is about 20 to 30 percent. Among survivors, 30 to 50 percent have serious neurologic, cognitive or psychiatric sequelae.⁷

• Available vaccine: Valneva’s IXIARO vaccine was approved by FDA in 2009. IXIARO is a vaccine indicated for active immunization to prevent the disease caused by JE virus. It is approved for use in individuals 2 months and older. The IXIARO vaccine is distributed directly to the U.S military and the private travel market.

Malaria

• Clinical description: Malaria in humans is caused by protozoan parasites of the genus Plasmodium (P), including P. falciparum, P. malariae, P. ovale and P. vivax. The bite of an infected female Anopheles mosquito transmits the Plasmodium species. Malaria occurs in large areas in Africa, Latin America, parts of the Caribbean, Eastern Europe, the South Pacific and Asia, including South Asia, Southeast Asia and the Middle East. Malaria is characterized by fever and influenza-like symptoms, including chills, headache, myalgias and malaise. In severe disease, acute kidney injury, acute respiratory distress syndrome, mental confusion, seizures, coma and death can occur.⁸

• Available vaccine: Sanaria Inc.’s PfSPZ-LARC2 (Late liver-stage Arresting, Replication Competent) vaccine is a third-generation injectable vaccine. It is expected to provide unparalleled protection rates even after a single dose, at doses 20 percent of Sanaria’s first-generation vaccine, thereby reducing the cost of goods five-fold.

Clinical trials for the company’s first- and second-generation vaccines have shown up to 100 percent protection for three months, sustained protection for two years without booster doses, and prevention against malaria infection in pregnant women for two years. These vaccines have been shown to be safe and well-tolerated in babies aged 5 months to adults aged 61-plus years.

Preclinical studies have shown that Sanaria’s LARC vaccines are significantly more potent and protective than other malaria vaccines. PfSPZ-LARC2 vaccination completely protects against infection in mouse models of malaria.

Sanaria plans to assess its PfSPZLARC2 vaccine’s safety and efficacy in diverse populations and environments in the United States, Burkina Faso and Germany in 2025. The results of these clinical trials are expected within a year.

Rabies

• Clinical description: Rabies is an acute, progressive and fatal encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus. The most common mode of rabies virus transmission is via the bite of a rabid animal. Lyssaviruses have been found on every continent except Antarctica. Rabies virus is classified into two major genetic lineages: canine and New World bat. Regionally, different viral variants are adapted to various mammalian hosts and perpetuate in dogs and wildlife such as bats, foxes, jackals, mongooses, raccoons and skunks. Canine rabies remains enzootic in many areas of the world, including Africa, parts of Central and South America and Asia. Clinical illness in humans culminates in an acute, fatal encephalitis. Approximately 80 percent of people with rabies will manifest with classic encephalitic disease in which fever, hydrophobia, hyperactivity and spasms eventually progress to paralysis and coma. Once clinical signs appear, patients die quickly in the absence of intensive supportive care.⁹

• Available vaccines:

– Bavarian Nordic A/S’s RabAvert has been used in the treatment of rabies for more than 35 years, both as a primary series of pre-exposure prophylaxis and for booster doses for post-exposure prophylaxis for all age groups. RabAvert is administered as an intramuscular injection and is approved to help prevent rabies infection before and after a suspected exposure.

– Sanofi’s IMOVAX was approved by FDA in 1980 and is indicated for all age groups. It has been studied across multiple clinical trials, demonstrating its safety, efficacy and tolerability. In pre-exposure prophylaxis studies, the vaccine has shown 97 to 100 percent seroprotection 21 to 28 days after vaccination and 100 percent seroprotection at three and six months. Sanofi is developing a next-generation rabies vaccine produced using serum-free Vero cells to expand vaccine supply and meet increasing demand. It will be highly purified and free from allergens and raw materials of animal or human origin.

Typhoid Fever

• Clinical description: Typhoid fever is caused by Salmonella enterica serotypes Typhi, Paratyphi A, Paratyphi B and Paratyphi C, which cause potentially severe and occasionally life-threatening illnesses. Typhoid fever and paratyphoid fever are acquired through the consumption of water or food contaminated by feces of an acutely infected or convalescent person or a person with chronic, asymptomatic carriage. The risk for infection is high in low- and middle-income countries with endemic disease, poor access to safe food and water and poor sanitation. Typhoid fever is prevalent in Asia — especially Pakistan, India and Bangladesh — Africa and Latin America. Symptoms include a high fever, headache, malaise, abdominal pain, constipation or diarrhea, dry cough, fatigue, myalgias and sore throat.¹⁰

• Available vaccines:

– Bavarian Nordic’s VIVOTIF is the only FDA-approved oral typhoid vaccine and is indicated for preventing typhoid fever in adults and children aged 6 years and older. It is administered in a series of four capsules over seven days and has demonstrated protection that can persist for up to five years following vaccination.

– Sanofi’s Typhim Vi vaccine was approved by FDA in 1994. It is indicated for individuals aged 2 years and older. Typhim Vi is used for active immunization to prevent typhoid fever caused by S typhi. The immunization consists of a single injection, and reimmunization should occur every two years under conditions of repeated exposure. Typhim Vi has shown 50 to 74 percent efficacy in two randomized double-blinded controlled clinical trials.

Yellow Fever

• Clinical description: Yellow fever (YF) is a single-stranded RNA virus that belongs to the genus Flavivirus. Vector-borne transmission of YF virus occurs via the bite of an infected Aedes or Haemagogus mosquito. YF virus has three transmission cycles: sylvatic (jungle), intermediate (savannah) and urban. Most YF disease in humans is due to sylvatic or intermediate transmission cycles. YF occurs in sub-Saharan Africa and tropical South America, where it is endemic and intermittently epidemic. Symptoms of YF range from a fever with backache, chills, headache, myalgia, nausea and vomiting, and prostration to hemorrhagic symptoms, jaundice and eventually shock and multi-system organ failure. The case fatality rate for severe cases is 30 percent to 60 percent.¹¹

• Available vaccine: Sanofi’s YF-VAX vaccine was approved by FDA in 1953. It is indicated for individuals 9 months of age and older. YF-VAX provides long-lasting protection following primary vaccination and is well-tolerated in most individuals. A YF vaccine certificate is required to enter several countries where YF is a concern. It becomes valid 10 days after vaccination with YF-VAX.

Zika Virus

• Clinical description: Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. Zika virus occurs through the bite of an infected Aedes mosquito. Zika virus occurs in tropical and subtropical regions, including the Pacific Islands, Southeast Asia and Brazil. Most Zika virus infections are either asymptomatic or result in mild clinical illness characterized by acute onset of fever, arthralgia, non-purulent conjunctivitis and maculopapular rash. Other symptoms can include edema, headache, lymphadenopathy, myalgia, retro-orbital pain and vomiting. Severe disease requiring hospitalization and death are both uncommon. Guillain-Barré syndrome and rare reports of encephalopathy, meningoencephalitis, myelitis, uveitis and severe thrombocytopenia have been associated with Zika virus infection. However, vertical transmission of the virus leads to congenital Zika virus infection; sequelae include microcephaly with brain anomalies and other severe neurologic consequences and fetal loss.¹²

• Available vaccine: Currently, there are no preventive vaccines available for the Zika virus. Valneva’s Zika VLA1601 second-generation vaccine is a highly purified inactivated vaccine candidate. The vaccine was developed on the original manufacturing platform of Valneva’s JE vaccine. Valneva initiated a Phase I clinical trial to investigate the safety and immunogenicity in individuals aged 18 to 49 years in March 2024. Topline data from this trial was expected in the first half of 2025.

Travel Vaccines in Development

Several global biotechnology companies are developing additional vaccines for these illnesses.

• Bavarian Nordic A/S. A biotechnology company headquartered in Denmark with facilities in the United States, Bavarian Nordic A/S has more than 30 years of experience as a vaccine developer and manufacturer and is a global leader in travel vaccines. It is focused on developing vaccines that address unmet medical needs in infectious diseases.

• Sanaria Inc. As a U.S.-based biotechnology company that develops and manufactures malaria vaccines, Sanaria Inc.’s mission is to develop whole-sporozoite (SPZ) vaccines that offer high-level, long-lasting protection against Plasmodium falciparum (Pf), the parasite responsible for more than 98 percent of deaths caused by malaria. Sanaria’s longterm goal is to develop a highly effective vaccine to be used as a linchpin of malaria elimination campaigns.

Sanaria has investigated other candidate vaccines: the PfSPZ vaccine, in which PfSPZ are attenuated by irradiation; the PfSPZ-CVac, in which infectious PfSPZ are attenuated by concomitant administration of an anti-malarial drug; and the PfSPZ-GA1, in which PfSPZ are attenuated by genetic alteration.

Stephen L. Hoffman, MD, CEO of Sanaria, says, “Our focus at Sanaria has been to develop vaccines to prevent the enormous morbidity and mortality caused by malaria among disadvantaged populations worldwide. We’re also focusing on developing a vaccine that could be used to prevent malaria in the 270 million travelers who visit areas with malaria annually, and especially the more than 40 million travelers who visit sub-Saharan Africa annually, who are at highest risk. Every year, about 3,000 travelers return to the U.S. with malaria and an average of 11 of these individuals die every year due to malaria acquired when traveling, primarily to Africa.”

• Sanofi. Sanofi is a multi-national pharmaceutical company headquartered in France, with facilities located in the United States. Sanofi is developing a next-generation YF vaccine, the world’s first YF vaccine produced using a cell culture process. A Sanofi spokesperson says, “With the increasing threat of climate-sensitive disease expansion, this next-generation [YF] vaccine will ensure a sustainable and robust vaccine supply for routine immunization. The innovative production process, utilizing Vero-cell technology, will significantly reduce the environmental impact of this vaccine, supporting the global agenda to mitigate climate change.” A Phase III clinical study for this vaccine is planned to start in 2025.

Thomas Grenier, head of North America vaccines at Sanofi, says, “For decades, Sanofi has been dedicated to protecting travelers through our comprehensive portfolio of vaccines, addressing some of the most critical health threats encountered during international travel. Our established vaccines for rabies, typhoid fever and [YF] have consistently demonstrated robust safety profiles and high efficacy, providing travelers with reliable protection when they need it most. We are investing in the development of next-generation vaccines for rabies and yellow fever to ensure a sustainable and robust supply, meeting the needs of global travelers for decades to come.”

• Valneva SE. A biotechnology company headquartered in France with offices in the United States, Valneva SE is a specialty vaccine company that develops, manufactures and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. It has commercialized three vaccines, including the world’s first chikungunya vaccine, to rapidly advance a broad range of vaccine candidates into and through the clinic, including a Zika candidate.

Plan Accordingly

By following the guidance outlined in the CDC Yellow Book 2024 and receiving appropriate travel vaccines, Americans can significantly reduce their risk of contracting these serious diseases when traveling outside the United States.