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A large study of an experimental vaccine for the world’s biggest infectious disease has finally kicked off in South Africa.

The Bill & Melinda Gates Medical Research Institute (MRI) will test a tuberculosis vaccine’s ability to prevent latent infections from causing potentially deadly lung disease. Last summer the nonprofit said it would foot $400 million of the estimated $550 million cost of running the 20,000-person Phase III trial.

It’s a pivotal moment for a vaccine whose origins date back 25 years when scientists identified two proteins that triggered strong immunity to the bacterium that causes tuberculosis. A fusion of those proteins, paired with the tree bark-derived adjuvant that helps power GSK’s shingles shot, comprise the so-called M72 vaccine.

After decades of failures in the field, the vaccine impressed scientists in 2018 when GSK found that it was 54% efficacious at preventing lung disease in a 3,600-person Phase IIb study.

But the Big Pharma decided that a full-blown trial was too expensive to conduct on its own. Gates MRI stepped in to license the vaccine in early 2020, right before the Covid pandemic shifted global vaccine priorities towards the coronavirus, further stalling the tuberculosis shot.

“There’s been frustration that it’s taken so long to get this trial up and running,” Thomas Scriba, deputy director of immunology for the South African Tuberculosis Vaccine Initiative, told Endpoints News last summer.

At last, the vaccine is getting a chance to prove itself in a bigger study. If successful, it could lead to the first new shot for tuberculosis in over a century.

Emilio Emini, CEO of the Gates MRI, told Endpoints that the initial results may come in roughly four to six years. “Hopefully this will galvanize a refocus on TB,” he said. “It’s been ignored for many, many years. We can’t ignore it anymore.”

A substantial impact

Even though an existing vaccine helps protect babies and children against severe tuberculosis, the bacterium responsible for the disease still causes roughly 10 million new cases and 500,000 deaths each year.

Emilio Emini

By vaccinating adolescents and adults who test positive for infections but don’t have symptoms of lung disease, the Gates MRI hopes the shot will help prevent mild infections from becoming severe ones, curtail transmission of the bug, which is predominantly driven by people with lung disease, and reduce deaths.

“The impact would be substantial,” Emini said. But he cautioned that the biology behind mild and severe diseases is still mysterious. “The reality is that no one really knows what keeps it under control.”

The study, which will take place at 60 sites across seven countries, will include some people who are not infected with tuberculosis to ensure that the vaccine is safe in that broader population.

“Having to pre-test everybody is not going to make the vaccine easy to deliver,” Emini said. If the vaccine is ultimately approved, it will likely be used in targeted communities with high tuberculosis, rather than across a whole country, he added. “In practice, you would immunize everybody in those populations.”

Emini described the Gates MRI’s rights to the vaccine as “close to a worldwide license.” GSK retained rights to commercialize the vaccine in certain countries but declined to specify which ones.

A spokesperson for GSK said that the company “has around 30 assets under development specifically for global health … none of which are expected to generate significant return on investment.”

“It is not sustainable or practical in the longer term for GSK to deliver all of these alone. So we continue to work on M72, but in partnership with others,” the spokesperson added.

If the shot works, Emini said that the Gates MRI will sublicense it to a manufacturer that will be responsible for making and marketing the vaccine. The details are still being worked out, he noted.

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Overview: The US dollar is surging today against most of the G10 currencies, and although the intraday momentum is stretched ahead of start of the North American session, there may be little incentive to resist before the end of the FOMC meeting tomorrow. The Bank of Japan's rate hike and the end of Yield Curve Control were not seen as the start of the tightening cycle. The two-year JGB yield slipped to a two-week low and settled below its 20-day moving average for the first time since mid-January. The Reserve Bank of Australia delivered a dovish hold by dropping the reference the future tightening. The yen (~-0.95%) and Australian dollar (~-0.85%) are the weakest of the G10 currencies. Emerging market currencies are lower, led by the Philippine peso (~-0.65%). The offshore yuan is weaker for the sixth consecutive session. 

Japanese, Australian, and New Zealand equities bucked the regional trend to advance today. Stoxx 600 in Europe is slightly lower, and if sustained, it would be the fourth consecutive losing session. That would be the long losing streak since last October. US index futures are nursing small losses. Ten-year JGB and Australian bond yield fell almost three basis points today. European benchmark yields are mostly slightly softer, though the periphery is lagging the core today. The US 10-year yield is little changed near 4.32%. The high for the year is near 4.35%. The US two-year yield did set a new high for the year yesterday near 4.75%. It is near 4.72% now. The greenback's strength is capping gold, which is trading inside yesterday's range and straddling the $2150 area. May WTI soared to $82.50 yesterday as its recent rally was extended amid Ukrainian strikes on Russian refiners. Diesel futures rose for the fourth consecutive session yesterday and gasoline futures extend its rally for a sixth session. May WTI is consolidating in a narrow range around $82. 

Asia Pacific

The Japanese press reports turned out to be fairly accurate: the Bank of Japan hiked its overnight target rate to 0%-0.1%. It scrapped the Yield Curve Control and confirmed it would stop buying ETFs. The one surprise was that the central bank indicated it would continue to purchase long-term bonds as needed. Governor Ueda, on one hand, said that the sustained 2% inflation target is not in hand, which sounded dovish. He also recognized that if the positive trends for wages and prices lift inflation expectations, and higher prices results, rate hikes may be necessary. The 10-year yield softened by almost three basis points (to ~0.73%). The Nikkei rallied 1%, and the yen was sold. The US dollar reached about JPY150.50.

As widely expected, the Reserve Bank of Australia left its cash target rate at 4.35%, where it has been since it was lifted by 25 bp last November. Economic activity has slowed, and price pressures are moderating, but the RBA seems to be in no hurry to unwind the November hike. Still, it dropped the reference to possible future hikes. The dovish hold sent the Australian dollar to a nine-day low near $0.6510. The futures market is not 100% confident the RBA will do so before September. However, the odds of an August cut have been marked up to around 97% from about 78% yesterday. 

The dollar is rising against the Japanese yen for the sixth consecutive session. It matches the longest advancing streak since last August and lifted the greenback to two-week highs near JPY150.70. The greenback approached JPY151 in mid-February through early March. The high from 2022 and 2023 was closer to JPY152. The intraday momentum indicators are stretched ahead of the North American open, but there may be little incentive to resist before tomorrow's FOMC meeting. What is being seen as a dovish hold by the RBA has sent the Australian dollar to nearly $0.6500. The trendline off the mid-February and early March lows comes in today a little below there. The low earlier this month was set slightly below $0.6480. The intraday momentum indicators are stretched. Initial resistance now is seen int he $0.6520-25 area. The greenback's gains, especially against the yen, have weighed on the Chinese yuan. The dollar is challenged the CNY7.20 cap that has not been violated this year. The PBOC set the dollar's reference rate at CNY7.0985 (CNY7.0943 yesterday). The Bloomberg average was CNY7.2020 (CNY7.1993 yesterday). The dollar is rising against the offshore yuan for the sixth consecutive session. It has reached CNH7.2130, its highest level in two weeks. The high for the year was set on February 14 near CNH7.2335.

Europe

The focus will not shift to Europe until Thursday. Three central banks meet then, Norway's Norges Bank, the Swiss National Bank, and the Bank of England. It is true the UK sees February CPI tomorrow. The year-over-year rate is expected to fall toward 3.5% from 4.0% and the core rate is seen falling to 4.6% from 5.1%. The UK's three-month annualized rate may near 2% and the six-month annualized increase maybe around 1.6%. Still, the market does not expect the BOE or the other west European central banks to change policy. Still, we suspect the risk is for a SNB move to get ahead of the ECB. The macro backdrop is conducive for a move with softer growth and low inflation. 

The March ZEW survey in Germany showed a little improvement. The assessment of the current situation remains poor. It edged up to -80.5 from -81.7. At its worst, during the pandemic, it fell to -93.5 in May 2020. It had recovered and peaked at 21.6 in October 2021, and had already begun weakening again before Russia's invasion of Ukraine. It was at -10.2 in January 2022. The expectations component is a different story. It rose for the eighth consecutive month to 31.7, which is the highest reading since February 2022. The high last year was set in February at 28.1.

The euro met sellers in the US morning yesterday as it pushed above $1.09. The selling knocked it down to new session lows near $1.0865 It has been sold to $1.0835 today, around where the (50%) retracement of the rally from the February 14 lows and the 200-day moving average are found. A break of this area targets $1.08. Note that in the futures market, the non-commercial (speculative) net long euro position has risen by 50% since the mid-February low through March 12 that is covered by the most recent CFTC report. Meanwhile, the non-commercial net long sterling position has risen every week this year but one, and at nearly 70.5k contracts (GBP62.5k per contract or almost $5.6 bln position), it is the largest net long position since 2007. Sterling extended its losses yesterday to nearly $1.2715, and has been sold to almost $1.2665 today, the lowest level since March 4. The $1.2670 area corresponds to the (61.8%) retracement of the recovery off the year's low set on February 14 near $1.2535. The intraday momentum indicators are stretched, but there is little chart support ahead of $1.2600.

America

The focus, of course, is on tomorrow's Fed meeting. No one expects the Fed to do anything. It is more about what the Fed says, and here, the dot plot is important. Keen interest is in the number of rates cuts the median dot signals. Three cuts were signaled in December. While CPI and PPI were slightly above market expectations, we do not think that they deviated much from what the Fed anticipated. To us, a key consideration is Fed Chair Powell's acknowledgement that officials did not need to see better data to boost their confidence that inflation was headed back to target. It just needed to see good data. Other macro forecasts may be tweaked. The 4.1% unemployment rate anticipated for this year looks low. It was at 3.9% in February. The median dot was for the headline and core PCE deflator to be at 2.4% at the end of the year. They stood at 2.4% and 2.8%, respectively in January and are expected to be unchanged when the February series is reported next week. The median dot in December was for the economy to grow 1.4% this year. The median forecast in Bloomberg's monthly survey was for 2.1% growth, which is the same as the IMF's projection. On tap today, February housing starts and permits, which are expected to tick up after weather-related weakness in January.

Canada reports February CPI today. Given the base effect, the 0.6% median forecast in Bloomberg's survey translates into a 3.1% year-over-year rate. It was at 2.9% in January. The low print in 2023 was in June at 2.8%. The underlying core measures are expected to be flat. The swaps market has about a 50% chance of a cut in June. It nearly fully discounted on March 5, the day before the Bank of Canada met. The summary of its deliberations will be published tomorrow. The market has about 60 bp of cuts discounted for this year, which is two quarter-point moves and around a 40% chance of a third. A 100 bp of cuts was fully discounted as recently as February 20.

The US dollar hovered around little changed levels against the Canadian dollar yesterday. Neither rising US equities (risk-on) nor an extension of oil's rally did much for the Canadian dollar. Resistance near CAD1.3550 has been overcome today and it the greenback looks poised to re-test the CAD1.36 area that capped the greenback in late February and earlier this month. A band of resistance extends toward CAD1.3620-25. Yesterday, the US dollar rose for the third consecutive session against the Mexican peso, which matches the longest advance in six months. The nearly 0.9% rally was the most since mid-January. Mexico was on holiday yesterday and the thin markets may have exacerbated the move. The US dollar rose to a six-day high of almost MXN16.87. This effectively recouped nearly half of the greenback's losses this month. Today, the dollar is approaching the next retracement (61.8%) and the 20-day moving average are near MXN16.93. Brazil was not closed and fell for the third consecutive session. In fact, the dollar poked above BRL5.03, its highest level since last November 1. Nearly all emerging market currencies fell yesterday. The South African rand (~-0.95%) was the weakest followed by the Mexican peso (~0.75%). Emerging market currencies are no match for the dollar's surge today. The MSCI Emerging Market Currency Index is off for the fifth consecutive session. 

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