Vaccine News

The World Health Organization (WHO) recently reported that measles outbreaks continue in various countries in 2024, such as India.

To alert international travelers, the U.S. Centers for Disease Control and Prevention (CDC) republished a global Watch-Level 1, Practice Usual Precautions, Travel Health Notice on August 14, 2024, identifying measles outbreaks in 56 countries.

Within the United States, the CDC has reported 219 measles cases in 27 jurisdictions this year, led by the states of Illinois and Oregon. Most of these cases are related to unvaccinated travelers.

The CDC writes that 'all international travelers should be fully vaccinated against measles with two doses of the measles-mumps-rubella (MMR) vaccine, including an early dose for infants 6–11 months.

However, the CDC does not recommend a third dose of MMR vaccination during or when visiting measles outbreaks.

In the U.S., MMR vaccines are available at most clinics and community pharmacies.

The Centers for Disease Control and Prevention (CDC) today issued a Health Alert Network Health Advisory (CDCHAN-00515) to notify clinicians and public health authorities of an increase in Oropouche virus disease cases confirmed in the Americas region.

The CDC issued this alert because the initial clinical presentation of the Oropouche virus may confuse providers as the symptoms are similar to those of dengue, Zika, and chikungunya.

Between January and August 1, 2024, more than 8,000 cases of Oropouche virus disease were reported, including two deaths and five cases of vertical transmission associated with fetal death or congenital abnormalities.

These Oropouche cases originate from endemic areas in the Amazon basin and regions in South America and the Caribbean.

The virus was first detected in 1955 in Trinidad and Tobago and is endemic in the Amazon basin. 

As of August 16, 2024, Brazil, Bolivia, Peru, Colombia, and Cuba were among the countries reporting cases. As testing and surveillance for Oropouche virus disease increase in the Americas, reports of cases from additional countries are expected.

Throughout 2024, travel-associated cases have been identified in travelers returning to the United States and Europe from Cuba and Brazil.

This CDC Health Advisory offers advice on evaluating and testing travelers who have been in impacted areas with signs and symptoms consistent with Oropouche virus infection.

It also raises awareness of the possible risk of vertical transmission (e.g., from gestational parent to fetus during pregnancy) and associated adverse effects on pregnancy.

The CDC issued a Level 2 Travel Health Notice in August 2024, suggesting pregnant women reconsider non-essential travel to areas with Oropouche virus outbreaks, such as Brazil and Cuba.

The new alert also highlights prevention measures to mitigate the additional spread of the virus and potential importation into unaffected areas, including the U.S.

Oropouche virus belongs to the Simbu serogroup of the genus Orthobunyavirus in the Peribunyaviridae family.

According to the CDC, approximately 60% of people infected with the Oropouche virus become symptomatic. The incubation period is typically 3–10 days. Providers should contact state, tribal, local, or territorial health departments to facilitate diagnostic testing.

As of August 2024, there are no approved Oropouche vaccines available.

The European Centre for Disease Prevention and Control (ECDC) today announced the likelihood of infection with mpox virus (MPXV) clade I for EU/EEA citizens traveling to or living in the affected areas and having close contact with affected communities is high, while the likelihood of infection is low when contacts with affected communities are avoided.

The severity of the mpox disease is expected to be low.

Overall, the ECDC's updated risk assessment for these populations is moderate and low, respectively.

“As a result of the rapid spread of this (mpox) outbreak in Africa, ECDC has increased the level of risk for the general population in the EU/EEA and travelers to affected areas. Due to the close links between Europe and Africa, we must be prepared for more imported clade I cases,” says Pamela Rendi-Wagner, Director of ECDC, in a press release.

As of August 16, 2024, the ECDC says to contain any possible clade 1 mpox outbreak in Europe, detecting cases and preventing secondary transmission is vital. This goal can be achieved through:

• Providing advice to travelers to affected areas on national guidance for vaccination against mpox before traveling. In many countries, the JYNNEOS® (MVA-BN®) vaccine is available. And offering travel advice to people visiting or returning from African countries with confirmed MPXV clade I outbreaks.
• Rapidly isolating suspected cases until proven negative and, if positive, until symptom resolution. And implementing contact tracing and testing close contacts of confirmed cases following ECDC testing protocols.
• Continuing risk communication activities and working with civil society organizations to engage population groups at higher risk of infection.

On August 14, 2024, the WHO Director-General determined that the increase of mpox clade 1 virus cases in African countries constitutes a new public health emergency.

In the United States, no clade 1 mpox cases have been detected by the U.S. CDC, and the JYNNEOS vaccine remains available.

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health announced topline results from a preliminary PALM 007 phase 2 clinical trial analysis.

The NIAID reported on August 15, 2024, that the study did not meet its primary endpoint of a statistically significant improvement in time to lesion resolution within 28 days post-randomization for patients with mpox who were administered SIGA’s oral tecovirimat (TPOXX®) a highly targeted antiviral treatment, versus placebo.

However, a meaningful improvement was observed in patients receiving tecovirimat whose symptoms began seven days or fewer before randomization and those with severe or more significant disease.

This study's finding is essential given Africa's ongoing clade 1 mpox virus outbreak.

“These data showing maximum benefit in patients treated early and with severe disease are entirely consistent with the mechanism of action of tecovirimat and with the studies in animals that led to U.S. FDA approval of this medicine for smallpox..... We believe these data warrant further investigation and support our view that post-exposure prophylaxis will be vital for the treatment of severe cases of mpox and all cases of smallpox,” stated Dennis Hruby, Chief Scientific Officer, in a press release.

On July 22, 2024, the U.S. government exercised a procurement option to deliver approximately $113 million in TPOXX treatment courses. 

TPOXX is currently available in the U.S., United Kingdom, Canada, and Europe. 

According to a recent article published by npj vaccines, infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers.

While there are six licensed prophylactic vaccines against HPV, none of them show any significant therapeutic effect on pre-existing infections.

Thus, a prophylactic vaccine endowed with therapeutic activity would afford protection regardless of the vaccine recipient's HPV infection status.

The key to eliminating virus-infected cells lies in anti-early HPV-encoded proteins, particularly anti-E6 or anti-E7 T-cell responses. 

This article describes the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (cPANHPVAX) relying on eight different HPV L2 peptide epitopes and the E7 oncoantigens from HPV16 and 18.

cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype.

These cytotoxic responses add to a potent, broad-coverage humoral (HPV-neutralizing) response.

cPANHPVAX safety was further improved by deleting the pRb-binding domains of E7.

These researchers wrote, 'this dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.'

Zhao, X., Zhang, Y., Trejo-Cerro, O. et al. A safe and potentiated multi-type HPV L2-E7 nanoparticle vaccine with combined prophylactic and therapeutic activity. npj Vaccines 9, 119 (2024). https://doi.org/10.1038/s41541-024-00914-z. 

Appili Therapeutics Inc. recently announced a product update for the first quarter of its fiscal year 2025, which ended on June 30, 2024.

“In recent months, we’ve achieved significant milestones by engaging regulatory authorities for ATI-1701 and ATI-1801, and together with our partner, Saptalis Pharmaceuticals, we launched our leading asset, LIKMEZ™ (ATI-1501),” said Don Cilla, President and CEO of Appili, in a press release on August 13, 2024.

“These achievements, together with ATI-1701 U.S. Air Force Academy (USAFA) funding commitments, are expected to enable us to execute our infectious disease programs and advance their development to bring these products to market for the benefit of patients and shareholders.”

ATI-1701, a novel live-attenuated vaccine for preventing F. tularensis, has secured $14 million in awards from the USAFA.    Tularemia is a potentially serious illness caused by the bacterium Francisella tularensis. People can become infected in several ways, including tick and deer fly bites and contact with infected animals.

Under the USAFA Cooperative Agreement, Appili will manage a comprehensive development program, including nonclinical studies, CMC/manufacturing, clinical preparatory, and regulatory activities supporting an IND submission in 2025. Appili has engaged with the U.S. Food and Drug Administration (“FDA”) via a pre-IND meeting, confirming the development pathway for ATI-1701, and is incorporating suggested changes into the development plan.

ATI-1801, a novel topical formulation of paromomycin (15% w/w), is under advanced clinical development for treating cutaneous leishmaniasis, a Neglected Tropical Disease, is a disfiguring skin infection affecting hundreds of thousands globally. Cutaneous and mucosal leishmaniasis can cause substantial morbidity; visceral and mucosal leishmaniasis can be life-threatening.

Appili is currently engaging with the FDA. In 2024, it submitted a type-B meeting request to discuss linking previously generated Phase 3 data and agreeing on the necessary registration package for a New Drug Application submission. ATI-1801 has received an Orphan Drug Designation from the FDA for certain forms of cutaneous leishmaniasis. 

In September 2023, Appili and its U.S. partner, Saptalis Pharmaceuticals LLC., announced the approval by the U.S. FDA of LIKMEZ™ (ATI-1501), a proprietary taste-masked liquid suspension formulation of metronidazole. LIKMEZ is the first FDA-approved ready-made suspension of metronidazole, addressing the unmet need in both pediatric patients and patients with dysphagia. Saptalis launched LIKMEZ in November 2023, and the product is available to patients and doctors in the U.S.